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1

Koca, Timur, Zuleyha Akgun, Serap Baskaya Yucel, Nihal Zerman Dag, and Mehmet Teomete. "Pregnancy a short time after multimodal therapy for bilateral breast cancer: A case report and review of literature." Journal of Oncology Pharmacy Practice 17, no. 4 (September 21, 2010): 440–43. http://dx.doi.org/10.1177/1078155210384755.

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Pregnancy occurring after multimodal therapy in a woman with breast cancer with a 1-year follow-up period is a relatively rare condition and has been defined as pregnancy-associated breast cancer. A patient can become pregnant after chemotherapy for breast cancer while she is on tamoxifen. However, the effects of tamoxifen on fetus and on the course of the pregnancy are still unknown. Here, we present a 39-year-old woman treated with chemotherapy and radiotherapy for bilateral breast cancer, and who became pregnant while taking tamoxifen.
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IONESCU, Olivia, and Nicolae BACALBASA. "Gestational breast cancer. Surgical treatment, pregnancy and fetal outcome." Romanian Journal of Medical Practice 12, no. 2 (March 31, 2017): 16–22. http://dx.doi.org/10.37897/rjmp.2017.1.3.

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Background. Gestational breast cancer (GBC) is also known as pregnancy-associated breast cancer and it comprises all the breast cancers (BCs) which are diagnosed either during pregnancy or in the first year after delivery or during the lactation period. At present it has been confirmed that the breast malignancies are the most common forms of cancer in pregnant women with a constant increase in its incidence because of the continuous postpone in childbearing especially in women older than 40 years. However, when diagnosed during the pregnancy, the treatment modalities of the BC are complex and difficult to establish as it must be considered the impact of the treatment both on the child and the course of pregnancy. Purpose. Using an online search on Pubmed, our aim was to make a review of the treatment possibilities of a pregnant woman presenting a breast malignant tumor. We have concentrated our paper on the surgical treatment and the possibility of an oncoplastic reconstruction types, the facts of radiotherapy during pregnancy and the prognosis of the GBC particularly in women who opt to continue the pregnancy. A resume of the epidemiology of GBG is also presented. Method. The following key words have been on Pubmed introduced: ,,breast cancer’’, ,,pregnancy’’, ,,staging”, ,,chemotherapy” and ,,radiotherapy”. As mentioned above, we have tried to select the BC cases diagnosed and treated during pregnancy for which the decision of the patient was to continue the pregnancy in spite of the diagnosis. We further aimed to present the prognosis of the pregnancy-associated BC, namely the pregnancy and fetal outcome, and to investigate if the decision to terminate the pregnancy is associated with a survival benefit. Conclusion. The surgical treatment of pregnancy-associated BC does not differ from that of non-pregnancy BC. Axillary LN-dissection is permitted while the data on the safety of sentinel-LN are still poor. Elective termination of the pregnancy has no impact on the overall survival of the patient.
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Upadhyay, Ruchi, Qurat-Ul-Ain Butt, Abraham Hamaoui, Cassandra Henderson, Sydney McCalla, and Hamid Gilak. "Triple Negative Breast Cancer in Pregnancy and Postpartum: Two Case Reports in Hispanic Women." Case Reports in Obstetrics and Gynecology 2015 (2015): 1–4. http://dx.doi.org/10.1155/2015/856931.

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Objective. Despite studies suggesting that triple negative breast cancer is more often seen in women of African ancestry, we report here two cases of pregnancy associated triple negative breast cancer in Hispanic women.Cases. Case one is a 37-year-old female para 2-0-0-2, who presented with a left breast mass, at 19 weeks of gestation, the biopsy of which reported an invasive ductal carcinoma, found to be triple receptor negative. The patient underwent chemotherapy during the pregnancy and was delivered with a cesarean at 37 weeks for obstetric indication. After delivery, the patient completed her chemotherapy that was followed by radical mastectomy and radiotherapy. Case two is a 28-year-old female para 6-0-1-5, who presented while breast-feeding with signs and symptoms of mastitis, and an engorged and tender right breast, five months postpartum. However, the sonogram revealed a fluid filled cavity. Aspiration and cytology did not reflect an infection and were negative for malignancy. High suspicion and lack of improvement led to biopsy that identified an invasive ductal carcinoma, found to be triple negative. The patient underwent chemotherapy followed by modified radical mastectomy.Conclusions. Triple negative breast cancer, during pregnancy or postpartum, poses a unique challenge and requires a multidisciplinary team to optimize treatment for these women.
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Galati, Francesca, Valentina Magri, Paula Andrea Arias-Cadena, Giuliana Moffa, Veronica Rizzo, Marcella Pasculli, Andrea Botticelli, and Federica Pediconi. "Pregnancy-Associated Breast Cancer: A Diagnostic and Therapeutic Challenge." Diagnostics 13, no. 4 (February 7, 2023): 604. http://dx.doi.org/10.3390/diagnostics13040604.

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Pregnancy-associated breast cancer (PABC) is commonly defined as a breast cancer occurring during pregnancy, throughout 1 year postpartum, or during lactation. Despite being a rare circumstance, PABC is one of the most common types of malignancies occurring during pregnancy and lactation, with growing incidence in developed countries, due both to decreasing age at onset of breast cancer and to increasing maternal age. Diagnosis and management of malignancy in the prenatal and postnatal settings are challenging for practitioners, as the structural and functional changes that the breast undergoes may be misleading for both the radiologist and the clinician. Furthermore, safety concerns for the mother and child, as well as psychological aspects in this unique and delicate condition, need to be constantly considered. In this comprehensive review, clinical, diagnostic, and therapeutic aspects of PABC (including surgery, chemotherapy and other systemic treatments, and radiotherapy) are presented and fully discussed, based on medical literature, current international clinical guidelines, and systematic practice.
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5

Poggio, Francesca, Marco Tagliamento, Chiara Pirrone, Davide Soldato, Benedetta Conte, Chiara Molinelli, Maurizio Cosso, Piero Fregatti, Lucia Del Mastro, and Matteo Lambertini. "Update on the Management of Breast Cancer during Pregnancy." Cancers 12, no. 12 (December 3, 2020): 3616. http://dx.doi.org/10.3390/cancers12123616.

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The diagnosis of breast cancer during pregnancy represents a challenging situation for the patient, her caregivers and physicians. Pregnancy adds complexity to oncological treatment planning, as many therapies can be potentially dangerous to the fetus. Therefore, a multidisciplinary approach is needed to offer a proper care for obtaining the best possible outcomes for the mother and the future child. Breast surgery is feasible throughout the pregnancy while radiotherapy should be postponed after delivery. Administration of chemotherapy is considered safe and can be given during the second and third trimesters, while it is contraindicated in the first trimester due to the high risk of fetal malformations. Endocrine therapy and targeted agents are not recommended during the whole pregnancy period; however, limited data are available on the use of the majority of new anticancer drugs in this context. The aim of the current review is to provide an update on the current state of art about the management of women diagnosed with breast cancer during pregnancy.
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6

Kufel-Grabowska, Joanna. "Fertility and breast cancer." Oncoreview 6, no. 4 (December 30, 2016): 0. http://dx.doi.org/10.5604/01.3001.0009.5057.

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Breast cancer is the most common cancer among females worldwide. The mean age of breast cancer patients is > 60 yrs old, and it is seldom found in women < 40 yrs old (6.5%) and in very young women < 35 yrs old (0.6%). In young females, fertility and all its aspects are an additional therapeutic challenge. Before initiating treatment, the oncologist should offer effective contraception to be applied throughout the therapy, bearing in mind that fertility preservation is of utmost importance. When it comes to breast cancer in pregnancy, the attending physician should use a therapy which is safe for both the mother and the foetus. Chemotherapy, radiotherapy, hormonal therapy and immunotherapy can, to a lesser or greater degree, damage the ovarian function resulting in amenorrhea in women < 50 yrs (33–76%). However, owing to fertility preservation strategies, more and more pregnancies are successful, even in breast cancer survivors.
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Simionescu, Anca A., Alexandra Horobeț, Lucian Belaşcu, and Dragoş Mircea Median. "Real-World Data Analysis of Pregnancy-Associated Breast Cancer at a Tertiary-Level Hospital in Romania." Medicina 56, no. 10 (October 6, 2020): 522. http://dx.doi.org/10.3390/medicina56100522.

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Background and objectives: Breast cancer is among the most common cancer types encountered during pregnancy. Here, we aimed to describe the characteristics, management, and outcomes of women with pregnancy-associated breast cancer at a tertiary-level hospital in Romania. Material and Methods: We retrospectively and prospectively collected demographic, oncological, and obstetrical data for women diagnosed with cancer during pregnancy, and who elected to continue their pregnancy, between June 2012 and June 2020. Complete data were obtained regarding family and personal medical history and risks factors, cancer diagnosis and staging, clinical and pathological features (including histology and immunohistochemistry), multimodal cancer treatment, pregnancy management (fetal ultrasounds, childbirth, and postpartum data), and infant development and clinical evolution up to 2020. Cancer therapy was administered following national guidelines and institutional protocols and regimens developed for non-pregnant patients, including surgery and chemotherapy, while avoiding radiotherapy during pregnancy. Results: At diagnosis, 16.67% of patients were in an advanced/metastatic stage, while 75% were in early operable stages. However, the latter patients underwent neoadjuvant chemotherapy rather than up-front surgery due to aggressive tumor biology (triple negative, multifocal, or HER2+). No patient achieved complete pathological remission, but only one patient relapsed. No recurrence was recorded within 12 months among early-stage patients. Conclusions: In this contemporary assessment of real-world treatment patterns and outcomes among patients with pregnancy-associated breast cancer, our findings were generally consistent with globally observed treatment outcomes, underscoring the need for a multidisciplinary team and reference centers.
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Wijaya, Ramesh, Wei Sean Yong, Allen WY Yeo, and Diana TH See. "Managing Breast Cancer Diagnosed in First Trimester Pregnancy: A Case Report." Annals of the Academy of Medicine, Singapore 36, no. 12 (December 15, 2007): 1024–27. http://dx.doi.org/10.47102/annals-acadmedsg.v36n12p1024.

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Introduction: Breast cancer is the most common malignancy in pregnant women, occurring at a rate of about 1 in 3000 pregnancies. Unfortunately, this will sometimes occur during the firsttrimester of pregnancy and this situation warrants discussion of management options with regard to the mother and child, especially with the current trend of deferring child bearing to a later age. Clinical Picture: We present a 34-year-old primigravida who had a breast lump prior to confirmation of her pregnancy and received her diagnosis of invasive breast cancer at 7 weeks’ amenorrhoea. The oncologic management options of this pregnant patient with breast cancer are discussed. Treatment: The patient eventually opted to undergo wide excision of the breast cancer with sentinel lymph node biopsy and possible axillary clearance together with termination of her pregnancy. Results: The patient successfully underwent surgery for her breast cancer and was subsequently treated with adjuvant therapy as per normal protocol for a non-pregnant patient. Conclusion: The management of breast cancer and pregnancy occurring concurrently is a complex problem fraught with many dilemmas for both the medical team, the patient and her family. The option chosen must involve a multidisciplinary team and have full informed consent of the patient. Key words: Adjuvant chemotherapy, Radiotherapy
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Pereira de Godoy, Jose Maria, Lívia Maria Pereira de Godoy, and Maria de Fatima Guerreiro Godoy. "Evolution Of Subclinical Systemic Lymphedema In-Patient With Lipedema And Axillary Dissection." International Journal of Medical Science and Clinical invention 7, no. 07 (July 4, 2020): 4868–70. http://dx.doi.org/10.18535/ijmsci/v7i07.02.

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Background: The surgical treatments of breast cancer associated or not with axillary drainage and radiotherapy constitute the main cause of secondary upper limb lymphedema. Obesity is a particularly aggravating aspect in patients with lymphedema. Novel concepts of subclinical systemic lymphedeman and clinical systemic lymphedema have recently been described. The aim of the present study was to evaluate the evolution of subclinical systemic lymphedema to upper limb lymphedema following treatment for breast cancer. Case: A 36-year-old female patient had been submitted to treatment for breast cancer involving left-side mastectomy and lymph node drainage during a pregnancy three years earlier. She had undergone both chemotherapy and radiotherapy. The patient had a portacath in the right arm for chemotherapy, which was removed after the first evaluation. She was submitted to bioelectrical impedance analysis, which revealed an increase in intracellular and extracellular water and body water in all limbs and the trunk above the normal range. The patient returned approximately two years after the initial evaluation, complaining of edema in the left arm. Conclusion: The treatment of breast cancer in patients with lipedema could lead to the development of subclinical lymphedema in patients with a BMI less than 30 kg/m2. Therefore, such conditions constitute a warning sign for the development of lymphedema.
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10

Alfasi, Ayelet, and Irit Ben-Aharon. "Breast Cancer during Pregnancy—Current Paradigms, Paths to Explore." Cancers 11, no. 11 (October 28, 2019): 1669. http://dx.doi.org/10.3390/cancers11111669.

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Breast cancer is the most common form of malignancy in pregnant women. The prevalence of pregnancy-associated breast cancer (PABC) is up to 0.04% of pregnancies and is expected to rise in developed countries. PABC represents a unique clinical scenario which requires a delicate balance of risks and benefits for both maternal and fetal well-being. Currently, there is paucity of data regarding the short- and long-term outcomes of in-utero exposure to anti-neoplastic agents. In general, when possible, treatment for PABC should follow the same guidelines as in non-pregnant patients. Surgery, including sentinel lymph node biopsy, is possible during all trimesters of pregnancy. Radiotherapy is contraindicated during pregnancy, although it might be considered in highly selected patients based on risk–benefit assessment. Evidence supports that administration of chemotherapy may be safe during the second and third trimesters, with cessation of treatment three weeks prior to expected delivery. Currently, hormonal therapy and anti-HER2 agents are contraindicated during pregnancy and should be postponed until after delivery. Prematurity is associated with worse neonatal and long-term outcomes, and thus should be avoided. While current data on the long-term effects of anti-neoplastic treatments are reassuring, grade of evidence is lacking, hence additional large prospective studies with long-term follow-up are essential to rule out any treatment-induced adverse effects.
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Lima, Candice, and Thiago L. Apolinario. "Abstract P3-02-01: Chemotherapy plus immunotherapy in stage IV triple-negative breast cancer patient during pregnancy: a case report." Cancer Research 83, no. 5_Supplement (March 1, 2023): P3–02–01—P3–02–01. http://dx.doi.org/10.1158/1538-7445.sabcs22-p3-02-01.

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Abstract Introduction Cancer during pregnancy is uncommon but the incidence is increasing, particularly in breast cancer, the most common tumor diagnosed in this scenario. The treatment decision in pregnant patients with triple-negative breast cancer is challenging, even more so in cases with advanced disease. Clinical case A 36-year-old woman was referred to our hospital in January, 2020 with the diagnosis of an early (T2N0M0, stage IIA) invasive carcinoma of no special type triple-negative tumor on the left breast and germinative CHEK2 mutation. She received neoadjuvant treatment with four cycles of ACdd followed by nine weeks of paclitaxel and carboplatin, interrupted for local disease progression. The patient underwent a nipple-sparing mastectomy plus sentinel lymph node biopsy without complications. The pathology report showed gross residual disease, so we decided on adjuvant treatment with radiotherapy followed by capecitabine. Twelve months after the end of the treatment, she received the diagnosis of second-trimester pregnancy but also presented suspicion of pulmonary, nodal, and liver relapse. The liver biopsy confirmed triple-negative histology with CPS &gt; 10. The first-line chemotherapy was liposomal doxorubicin, which showed hepatic disease progression after two cycles. As second-line, we started carboplatin, gemcitabine, and pembrolizumab. The radiologic evaluation after two cycles showed a partial response in the lung and liver, with the patient presenting excellent tolerability without fetal complications. The treatment plan is to wait until the term for delivery and continue treatment until progression or toxicity. Conclusion We report the first stage IV triple-negative breast cancer case in a pregnant patient treated with chemotherapy plus immunotherapy. This case indicates that the treatment is feasible and should be considered in this scenario. Citation Format: Candice Lima, Thiago L. Apolinario. Chemotherapy plus immunotherapy in stage IV triple-negative breast cancer patient during pregnancy: a case report [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-02-01.
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Findeklee, Sebastian. "Overview Tumour Disease and Oncologic Therapy During Pregnancy." Zeitschrift für Geburtshilfe und Neonatologie 222, no. 02 (February 1, 2018): 61–65. http://dx.doi.org/10.1055/s-0044-100259.

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AbstractNewly diagnosed cancer in pregnancy is an issue with increasing importance, because fulfilling the wish to have a child is shifted later in life. Tumour disease is diagnosed in around 0.1% of all pregnancies in Germany. Most common tumour entities involve the breast, the cervix and the hematopoietic system. As tumour prognosis is not negatively affected by pregnancy and gestation does not disclude oncologic therapy it is important to plan treatment immediately. Oncologic surgery preserving the uterus is not at all limited. Chemotherapy with anthracyclines, taxanes or platinum derivates is possible from the second trimenon on. Only radiotherapy should be avoided during pregnancy. Before initiating therapy, fertility preserving methods like cryopreservation of oocytes and/or ovarian tissue should be offered to the patient. Preterm birth is more common in women with a first diagnosis of cancer during pregnancy. Other negative effects on the child’s future are not yet known. Treatment of pregnant cancer patients should be handled by experienced centres with a multi-professional team.
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Martinez Pineda, Wendy Jazmin, Angel Luis Calva Espinosa, Alicia Guillermina Gonzalez Noguez, Carlos Osorio Solis, and Alvar Jose Vacio Olguin. "Tonsil cancer treated with radiotherapy during a pregnancy: a case report." Journal of Radiotherapy in Practice 19, no. 2 (August 27, 2019): 197–201. http://dx.doi.org/10.1017/s1460396919000608.

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AbstractIntroduction:Cancer during pregnancy has an incidence of 1/1,000, and when diagnosed, the most common ones are breast cancer (1/10,000), Hodgkin’s lymphoma (1/6,000), and head and neck cancer (1/10,000). If a diagnosis is made during pregnancy, the treatment cannot wait until delivery, and there is concern about the effects that radiotherapy may have on the foetus. The multidisciplinary group has to assess and ethically make decisions with regard to the mother and foetus.Clinical case:A 35-year-old female, a carrier of Behcet’s disease, underwent 5 years of treatment with hydroxychloroquine, prednisone and low-molecular-weight heparin (the patient being a carrier of Behcet’s disease, there is a high risk for cancer of the oral cavity and oropharynx with an HR of 2·11, so the cancer could be related to the tonsil). The patient’s oncological situation started on December 2017 with a volume increase in preauricular, parotid and right mandibular angle, with a progressive growth. At this time, the foetus was of 17·5 weeks of gestation. An oral cavity tumour that invaded the right retromolar triangle was observed, and upon biopsy, a basaloid squamous cell carcinoma was diagnosed.Radiotherapy treatment was started at 22 weeks of gestation; intensity-modulated radiation therapy (IMRT) was planned with a dose of 69·96 Gy to the primary tumour and 59·4 Gy to ganglion levels II, III and IV, bilaterally in 33 fractions. At fraction 27 a significant decrease in tumour volume was noted, so adaptive radiotherapy was performed to complete the treatment. Currently the patient has no clinical evidence of tumour pathology.Discussion:The risk of radiation exposure in pregnant women (after 20 weeks of gestation), being treated for cancers of the tonsil, reaching the foetus is minimal, with a reduced risk of a few or no effects.Conclusions:Radiotherapy in tonsil cancer has been shown to be effective in combination with chemotherapy for local control of the disease. In the case of this pregnant patient, radiotherapy, as the only modality, provided local control and little exposure of radiation to the foetus.
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Dasic, Davor, Narendra K. Rath, Mario Ganau, and Zaid Sarsam. "Management Challenges of Metastatic Spinal Cord Compression in Pregnancy." Case Reports in Surgery 2020 (November 1, 2020): 1–11. http://dx.doi.org/10.1155/2020/8891021.

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Primary and secondary spinal tumours with cord compression often represent a challenging condition for the patient and clinicians alike, even more so during pregnancy. The balance between safe delivery of a healthy baby and management of the mother’s disease bears many clinical, psychological, and ethical dilemmas. Pregnancy sets a conflict between the optimal surgical and oncological managements of the mother’s tumour and the well-being of her foetus. We followed the CARE guidelines from the EQUATOR Network to report an exemplificative case of a 39-year-old woman with a 10-year history of breast cancer, presenting in the second trimester of her first pregnancy with acute onset severe thoracic spinal instability, causing mechanical pain and weakness in lower limbs. Neuroradiological investigations revealed multilevel spinal deposits with a pathological T10 fracture responsible for spinal cord compression. The patient was adamant that she wanted a continuation of the pregnancy and her baby delivered. After discussion with her oncologist and obstetrician, we agreed to perform emergency spinal surgery—decompression and instrumented fixation. The literature search did not reveal a similar case of spinal metastatic breast cancer undergoing spinal instrumentation and delivery of a healthy baby a few months later. Following the delivery, the patient had further oncological treatment, including chemotherapy and radiotherapy. The paucity of such reports prompted us to present this case and highlight the relevance of a multidisciplinary approach involving obstetrician, oncologist, spinal surgeon, and radiologist to guide the optimal decision-making process.
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Amant, Frédéric, Gunter von Minckwitz, Sileny N. Han, Marijke Bontenbal, Alistair E. Ring, Jerzy Giermek, Hans Wildiers, et al. "Prognosis of Women With Primary Breast Cancer Diagnosed During Pregnancy: Results From an International Collaborative Study." Journal of Clinical Oncology 31, no. 20 (July 10, 2013): 2532–39. http://dx.doi.org/10.1200/jco.2012.45.6335.

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Purpose We aimed to determine the prognosis of patients with breast cancer diagnosed during pregnancy (BCP). Patients and Methods In this cohort study, a multicentric registry of patients with BCP (from Cancer in Pregnancy, Leuven, Belgium, and GBG 29/BIG 02-03) compiled pro- and retrospectively between 2003 and 2011 was compared with patients who did not have associated pregnancies, using an age limit of 45 years. Patients with a diagnosis postpartum were excluded. The main analysis was performed using Cox proportional hazards regression of disease-free survival (DFS) and overall survival (OS) on exposure (pregnant or not), adjusting for age, stage, grade, hormone receptor status, human epidermal growth factor 2 status, histology, type of chemotherapy, use of trastuzumab, radiotherapy, and hormone therapy. Results The registry contained 447 women with BCP, mainly originating from Germany and Belgium, of whom 311 (69.6%) were eligible for analysis. The nonpregnant group consisted of 865 women. Median age was 33 years for the pregnant and 41 years for the nonpregnant patients. Median follow-up was 61 months. The hazard ratio of pregnancy was 1.34 (95% CI, 0.93 to 1.91; P = .14) for DFS and 1.19 (95% CI, 0.73 to 1.93; P = .51) for OS. Cox regression estimated that the 5-year DFS rate for pregnant patients would have increased from 65% to 71% if these patients had not been pregnant. Likewise, the 5-year OS rate would have increased from 78% to 81%. Conclusion The results show similar OS for patients diagnosed with BCP compared with nonpregnant patients. This information is important when patients are counseled and supports the option to start treatment with continuation of pregnancy.
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Rajan, Kiran Kasper, Katherine Fairhurst, Beth Birkbeck, Rebecca Wilson, Jelena savovic, Chris Holcombe, and Shelley Potter. "Abstract PD15-04: PD15-04 Overall survival following breast conserving surgery and adjuvant radiotherapy compared with mastectomy for early stage breast cancer: a systematic review and meta-analysis." Cancer Research 83, no. 5_Supplement (March 1, 2023): PD15–04—PD15–04. http://dx.doi.org/10.1158/1538-7445.sabcs22-pd15-04.

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Abstract Background Breast conserving surgery with adjuvant radiotherapy (BCS+RT) and mastectomy are currently offered as oncologically equivalent options for the surgical management of early breast cancer based on findings from randomised controlled trials (RCTs) conducted over four decades ago. Since then, locoregional and systemic breast cancer treatments have improved significantly and several recent observational studies suggest a survival advantage in patients receiving BCS+RT compared to those having mastectomy. If BCS+RT is oncologically superior to mastectomy, this may dramatically impact surgical treatment recommendations. The aim of this systematic review was to identify, critically appraise and summarise the contemporary literature comparing survival following BCS+RT and mastectomy to inform surgical decision-making for patients with early breast cancer. Methods A systemic search of MEDLINE, Cochrane Central Register of Controlled Trials and Embase identified studies published between 1st January 2000 to 22nd September 2021. Included were primary research studies published in English comparing overall survival in women undergoing primary surgery with either BCS+RT or mastectomy for unilateral stage I to III breast cancer. Excluded were studies evaluating neoadjuvant chemotherapy; rare breast cancer subtypes (e.g. mucinous) or in specific patient populations (e.g. pregnancy associated breast cancer) and those that completed recruitment before 1st January 1990. We used the ROBINS-I tool to assess the risk of bias in study results and GRADE to assess the overall certainty of evidence. All papers without critical risk of bias were included in a quantitative meta-analysis. Where more than one study reported outcomes in overlapping population-based registry cohorts, the study with the most recent data on the largest cohort was selected for analysis. The primary analysis was a random effects meta-analysis with a fixed effect model undertaken as sensitivity analysis. A secondary meta-analysis was performed for studies only including triple negative breast cancers. All analyses were conducted using STATA17. Results 10,876 abstracts were screened and 157 full-text papers assessed for eligibility, of which 93 (17 multi-centre observational studies, 30 were single-centre observational studies and 46 registry-based studies) met the inclusion criteria for the review. 25 papers were excluded from meta-analysis due to an overall critical risk of confounder bias and 27 were excluded due overlapping study populations. 36 studies (34 with serious risk of bias and 2 with moderate risk of bias) reporting survival outcomes on 1,321,291 patients (729,789 undergoing BCS+RT and 591,502 undergoing mastectomy) were included in the meta-analysis. The pooled hazard ratio was 0.72 (95% CI 0.64– 0.81, p&lt; 0.001, I2 97.6%) demonstrating improved overall survival for patients undergoing BCS+RT compared with those receiving mastectomy. The sensitivity analysis, using a fixed effect model, showed a hazard ratio of 0.88 (95% CI 0.87 – 0.89, p&lt; 0.001, I2 97.6%) for survival in women undergoing BCS+RT compared with mastectomy. Meta-analysis of 8 studies reporting survival in 17,181 patients with triple negative breast cancer showed a hazard ratio of 0.73 (95% CI 0.68 – 0.79), p&lt; 0.001, I2 34.7%) for those receiving BCS+RT versus mastectomy. Discussion This meta-analysis provides further, albeit very low certainty evidence, that overall survival is improved following BCS+RT compared with mastectomy in a contemporary cohort of patients treated for early-stage breast cancer. These results should be interpreted with caution due to the heterogeneity of included studies and the high risk of bias associated with observational data. As future RCTs will not be feasible, well-designed large-scale prospective observational studies are needed to provide better evidence to support surgical decision-making in early-stage breast cancer. Citation Format: Kiran Kasper Rajan, Katherine Fairhurst, Beth Birkbeck, Rebecca Wilson, Jelena savovic, Chris Holcombe, Shelley Potter. PD15-04 Overall survival following breast conserving surgery and adjuvant radiotherapy compared with mastectomy for early stage breast cancer: a systematic review and meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-04.
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Mouh, Fatima Zahra, Meriem Slaoui, Rachid Razine, Mohammed EL Mzibri, and Mariam Amrani. "Clinicopathological, Treatment and Event-Free Survival Characteristics in a Moroccan Population of Triple-Negative Breast Cancer." Breast Cancer: Basic and Clinical Research 14 (January 2020): 117822342090642. http://dx.doi.org/10.1177/1178223420906428.

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Introduction: Triple-negative breast cancer (TNBC) is a group of breast carcinoma characterized by the lack of expression of estrogen and progesterone hormone receptors (ER, PgR) and HER2. This form is also characterized by its aggressiveness, a low survival rate, and the absence of targeted therapies. This study was planned to evaluate the clinical features, treatment, and prognosis characteristics of TNBC in a population of Moroccan patients. Methods: In this retrospective study, a total of 905 patients diagnosed with breast cancer at the National Institute of Oncology in Rabat, Morocco, have been included. Based on molecular subtype, patients were divided into 2 categories: TNBC and non-TNBC patients. Data were recorded from patients’ medical files and analyzed using SPSS 13.0 software (IBM). Results: Overall, 17% of the patients had TNBC. At diagnosis, the median age of TNBC cases was 47 years, with extreme ages of 40 and 55 years. The median follow-up time was 30 months (10-53 months) and the 3-year survival rate was 76%. No significant difference was observed among the patients in terms of age at diagnosis, age at menarche, age at the time of first birth, nulliparity, oral contraception, and family history of breast cancer. Menopausal status and the number of pregnancy were significantly higher in the non-TNBC group. The percentage of grade 3 (G3) tumors was higher in the TNBC group ( P < .001). Using neoadjuvant, adjuvant chemotherapy and radiotherapy, a net benefit in the event-free survival was registered for the 2 groups. Conclusions: This retrospective study was very informative and showed that women with TNBC had a less favorable prognosis than non-TNBC cases. Clinical data demonstrated that risk factors including age, premenopausal status, parity, hormonal contraceptive use, advanced disease, and a high histologic grade were independently associated with TNBC. However, large tumors and high Scarff-Bloom and Richardson grade prevail in TNBC cases with a higher incidence of lymph node metastases.
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Turner, Nicholas C., David W. Cescon, Sibylle Loibl, Wolfgang Janni, Hope Rugo, Judith Balmaña, Cheynna Crowley, et al. "Abstract OT2-24-02: ZEST: Randomized phase III study evaluating efficacy and safety of niraparib in patients with HER2-negative BRCA-mutated or triple-negative breast cancer with detectable circulating tumor DNA after definitive therapy." Cancer Research 82, no. 4_Supplement (February 15, 2022): OT2–24–02—OT2–24–02. http://dx.doi.org/10.1158/1538-7445.sabcs21-ot2-24-02.

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Abstract Background: Following definitive treatment, there is no standard-of-care for patients (pts) with HR+HER2− breast cancer (BC) or TNBC beyond clinical monitoring for metastasis. Recurrence rates remain high for pts with a greater burden of residual disease after neoadjuvant chemotherapy. Detectable circulating tumor DNA (ctDNA) is also associated with a high risk of clinical relapse. However, there is no standard therapy for pts with detectable ctDNA who have not yet developed clinical metastasis. Niraparib, a poly(ADP-ribose) polymerase inhibitor (PARPi), inhibits repair of DNA damage and stalled replication forks. PARPi showed clinical activity in pts with TNBC, with increased responses in homologous recombination deficient (HRd) tumors. HRd is common in TNBC, including in pts with wild-type or mutated tumor BRCA (tBRCAwt and tBRCAm). Neoadjuvant niraparib showed clinical activity in tBRCAm HER2− BC. This study will assess niraparib in pts with tBRCAm HER2− BC or tBRCAwt TNBC who have detectable ctDNA after completion of definitive therapy. Trial Design: ZEST (NCT04915755) is a multicenter, multicohort, Phase 3, double-blind, placebo-controlled study in pts with tBRCAm HER2− BC (HR+ with concomitant endocrine therapy and TNBC; Cohort 1) or tBRCAwt TNBC (Cohort 2) with detectable ctDNA following surgery or completion of adjuvant chemotherapy and radiotherapy. Pts who previously completed definitive therapy at any time are eligible for ctDNA monitoring and potential enrollment in the trial following detection of ctDNA. HR+/HER2− pts must have known tBRCAm to qualify for ctDNA screening. For all other pts, tBRCA status will be confirmed in those with detectable ctDNA. HRd status will be assessed at prescreening; pts with tBRCAwt TNBC and HRd will be allocated to Cohort 2. Pts with detectable ctDNA and no recurrence on staging scans will be randomized 1:1 to receive niraparib or placebo. Niraparib will be given orally once daily at a dose of 300 mg; pts with body weight &lt;77 kg, platelet count &lt;150,000/µL, or with moderate hepatic impairment will receive 200 mg. Pts will be monitored with CT imaging every 12 weeks for the first 2 years, then every 6 months. Treatment will continue until disease recurrence, death, or unacceptable toxicity. All pts will be stratified by time from last intervention to randomization (&lt;6 vs ≥6 months) and stage of BC (stage I/II vs III). Pts in Cohort 1 will also be stratified by HR status and pts in Cohort 2 by prior use of adjuvant capecitabine. Table 1 shows key eligibility criteria. The primary endpoint is disease-free survival for niraparib versus placebo; secondary objectives include overall survival, time to progression on next anticancer therapy, distant recurrence-free survival, safety, tolerability, and health-related quality of life. The primary efficacy analyses will be based on all randomized pts. Safety will be analyzed in all randomized pts who receive ≥1 dose of niraparib. Target accruals are 200 and 600 pts in Cohorts 1 and 2, respectively. The trial has begun enrolling. Funding: GlaxoSmithKline (GSK) study 213831; NCT04915755. Medical writing support was provided by Fishawack Indicia, part of Fishawack Health, funded by GSK. Table 1.Key eligibility criteriaInclusion criteriaExclusion criteria• Age ≥18 years• Prior treatment with a poly(ADP-ribose) polymerase inhibitor. • Current treatment with a cyclin-dependent kinase 4 and 6 inhibitor or endocrine therapy other than anastrozole, letrozole, exemestane, and tamoxifen. • Any sign of local recurrence or metastasis. • Lack of definitive response to preoperative chemotherapy by pathologic or radiographic evaluation, in cases where preoperative chemotherapy was administered. • Live vaccine therapy within 30 days of planned start of study randomization. • A second primary malignancy, except (a) adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ of the breast, Stage I Grade 1 endometrial carcinoma; (b) other solid tumors and lymphomas (without bone marrow involvement) diagnosed ≥5 years prior to randomization and treated with no evidence of disease recurrence, and for whom no more than 1 line of chemotherapy was applied. • Pregnancy, breastfeeding, or expecting to conceive children while receiving study treatment and/or for up to 180 days after the last dose of study treatment • History of human immunodeficiency virus • Known history of myelodysplastic syndrome or acute myeloid leukemia• Stage I-III breast cancer, with surgical resection of the primary tumor, that is confirmed as either: o triple-negative breast cancer, irrespective of tumor breast cancer gene (tBRCA) status, or o Hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)- with a documented tBRCA mutation. • Completed prior standard therapy for curative intent including all of the following, if indicated: neoadjuvant treatment, surgery, adjuvant radiotherapy, and adjuvant chemotherapy. • Stable regimen of endocrine therapy, if indicated, for ≥3 months prior to enrollment (HR+ only) • Detectable circulating tumor DNA by central Signatera testing. • An archival tumor tissue specimen of the primary tumor sufficient in quality and quantity for ctDNA assay design and tBRCA and homologous recombination deficiency (HRD) testing Citation Format: Nicholas C Turner, David W Cescon, Sibylle Loibl, Wolfgang Janni, Hope Rugo, Judith Balmaña, Cheynna Crowley, Jon Chung, Giulia Fucli, Erin Hofstatter, Tara Frenkl, Melinda L Telli. ZEST: Randomized phase III study evaluating efficacy and safety of niraparib in patients with HER2-negative BRCA-mutated or triple-negative breast cancer with detectable circulating tumor DNA after definitive therapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-24-02.
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Mustață, Laura, Nicolae Gică, Radu Botezatu, Raluca Chirculescu, Corina Gică, Gheorghe Peltecu, and Anca Maria Panaitescu. "Malignant Phyllodes Tumor of the Breast and Pregnancy: A Rare Case Report and Literature Review." Medicina 58, no. 1 (December 26, 2021): 36. http://dx.doi.org/10.3390/medicina58010036.

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Phyllodes Tumor (PT) is a rare fibroepithelial breast tumor that can behave differently depending on its biologic features. Traditionally, PTs are classified by their histologic features into benign, borderline, and malignant. In most cases that were reported, all PTs may recur, but only the borderline and malignant PT can metastasize. PT usually occurs as a breast lump or accidental finding on ultrasound (US) examination. The clinical features include a well-defined breast mass, regular or lobulated. The diagnosis is based on the integration of morphology features, but remains challenging, particularly in the distinction from fibroadenomas. We report a case of a 36-year-old patient who presented for a voluminous breast mass, rapidly growing in the past 3–4 months. At presentation, the patient was 19 weeks pregnant. The breast tumor had the clinical and US aspect of PT. A core needle biopsy was obtained, confirming a benign PT, and local excision was performed with no postoperative complications. The final pathology report showed a borderline PT with close resection margins of 1 mm. Immunohistochemistry (IHC) established the diagnosis of malignant PT with heterologous sarcomatous differentiation. The case was discussed in the multidisciplinary tumor board (MDT) and mastectomy was recommended. The patient fully consented but refused surgery at 25 weeks’ gestation, fearing premature delivery. The right breast was closely monitored by US, and at 9 weeks after the first surgery, signs of local recurrence were detected. At 35 weeks’ gestation, right mastectomy was performed, with no perioperative complications. The pregnancy was closely followed up and no complication were found. The final pathology report describes multiples PT recurrences with heterologous sarcomatous differentiation. The pregnancy outcome was uneventful, and the patient delivered a healthy child vaginally at term with no peripartum complication. Postpartum, a computer tomography (CT) examination of the head, thorax, abdomen and pelvis was performed, with no evidence of metastases. Adjuvant chemotherapy and radiotherapy completed the treatment. The follow-up and CT scan showed no metastases or further recurrence 4 years after diagnosis. In conclusion, diagnosis of PT can be difficult, especially because of the easy confusion with fibroadenoma of the breast. There are rare cases when a pathology exam needs further assessment and IHC is recommended for accurate diagnosis. Although malignant PT is rare and accounts for <1% of all breast cancers, the diagnosis and treatment that are recommended are based on the reported cases. Moreover, when complete surgical excision is achieved, the rates of recurrence and distant metastases are low, and adjuvant therapy might not be necessary.
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Cabıoğlu, Neslihan, Hasan Karanlik, Mehmet Ali Gulcelik, Abdullah İgci, Mahmut Muslumanoglu, Havva Belma Kocer, Cihan Uras, et al. "Abstract PD15-01: PD15-01 AXILLARY NODAL RECURRENCE IS RARE IN PATIENTS WITH NODE-POSITIVE BREAST CANCER UNDERGOING SLNB FOLLOWING NEOADJUVANT CHEMOTHERAPY : EARLY RESULTS OF THE NEOSENTITURK-TRIAL/MF-18-03." Cancer Research 83, no. 5_Supplement (March 1, 2023): PD15–01—PD15–01. http://dx.doi.org/10.1158/1538-7445.sabcs22-pd15-01.

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Abstract Background: Whether axillary lymph node dissection (ALND) following sentinel lymph node biopsy (SLNB) could be spared in patients with initially clinically positive axilla after neoadjuvant chemotherapy (NAC) is still controversial even though recent studies indicate that axillary recurrence seems to be a rare event. Our aim is to find out whether omitting ALND could be oncologically safe in patients undergoing SLNB after NAC. Material and Methods: Of patients presented with c T1-4N1-3M0 disease, those undergoing SLNB after NAC were included in the prospective multicentre registry trial " MF18-03/BHWG" (ClinicalTrials.gov/NCT04250129). Cases with inflammatory breast cancer, distant metastases, pregnancy, bilateral breast cancer, or other cancers and those without adjuvant nodal radiotherapy were excluded from the study. The end points of the present report are the axillary nodal recurrence (AR) and locoregional recurrence (LRR) rates at a median follow-up more than 2 years, and determine factors associated with AR and LRR . The locoregional recurrences included ipsilateral, and contralateral axillary recurrences, infra-and supraclavicular recurrences, and recurrences in the mammaria interna region. Results: Between January 2018 to January 2021, 2358 patients with cN(+) disease, who became cN0 after NAC, and underwent SLNB, were analyzed. Median age was 47 (range, 21-86). Of those, the majority of patients had cT1-2 (80.5%) and N1 (80.3%) disease. Following NAC, half of the patients (50%) had breast conserving surgery, whereas the remaining half had mastectomy (50%). Of 2358 patients, 908 (38.5%) had ALND following SLN (ypN+, 85%) and 1450 (61.5%) underwent SLNB alone (ypN0, 72%). SLNB was performed by using the blue dye technique-alone in 66.6% of patients and by targeted axillary dissection in 659 patients (27.9%). Of those, 819 (34.8%) were HER2(+) and 373 (15.8%) were triple negative. The pCR rates for the axilla, breast and both for the axilla and breast were 50%, 35% and 28%, respectively. At a median follow-up time of 28 months (range, 12-62), the LRR, AR and isolated AR rates were 0.6% (n=14), 0.25% (n=6) and 0.13% (n=3), respectively. Furthermore, no significant difference could be found in LRR- and AR- rates between SLNB-alone and ALND groups regardless of the definitive nodal pathology (Table 1). Nodal recurrences were seen at a median of 12 months after the surgery. Of 6 cases with AR, 3 had synchronous local recurrences in breast, and 2 of them also had lung metastases in addition to local recurrence. All patients with AR were interestingly found to have HER2(+) or triple negative breast cancer at the initial diagnosis, and had residual invasive cancer in the breast surgical specimen. Logistic regression analyses revealed that patients with AR were significantly more likely to be younger than 45 (RR=7.81 ; 95% CI, 0.91-66.91) and have a cN2-3 (RR=4.1; 95% CI, 0.83-20.38), and non-luminal breast cancer (RR=12.47; 95% CI, 1.45-106.9) at the initial diagnosis (Table 2). Similarly, patients with LRR were more likely to present with cN2-3 disease (RR=3.09; 95% CI, 1.07-8.94) and non-luminal pathology (RR=6.27; 95%CI, 1.96-20.06) . Conclusion: This large prospective registry data also suggest that nodal recurrences can be detected at very low rates within 3 years after surgery in patients with clinically node-positive disease following NAC regardless of the extent of axillary surgery or nodal pathology as long as regional nodal radiation is provided. Since patients with early nodal recurrences have an agressive tumor biology with a potential of systemic recurrences, effective adjuvant systemic therapies should be considered in those with HER2(+) or triple negative residual breast cancer after surgery following adjuvant nodal radiation. Table 1. Local locoregoinal and systemic recurrences in cT1-4N1-3 patients with ypN0/ypN(+) diseases (n =2358) Table 2. Factors associated with axillary and locoregoinal recurrences (AR = axillary recurrences, LRR = locoregoinal recurrences, pCR = pathologic complete response) Citation Format: Neslihan Cabıoğlu, Hasan Karanlik, Mehmet Ali Gulcelik, Abdullah İgci, Mahmut Muslumanoglu, Havva Belma Kocer, Cihan Uras, Gokhan Giray Akgul, Mustafa Tukenmez, Serkan Ilgun, Didem Can Trabulus, Guldeniz Karadeniz Cakmak, Ahmet Dağ, Nilufer Yıldirim, Baha Zengel, Ebru Sen Oran, Kazim Senol, Halil Kara, Selman Emiroglu, M. Umit Ugurlu, Bulent Citgez, Yeliz Emine Ersoy, Atilla Celik, Ece Dilege, Yasemin Bolukbaşı, Niyazi Karaman, Gul Basaran, Aykut Soyder, Ayfer Kamali Polat, Gurhan Sakman, Serdar Ozbas, Ayse Altınok, Leyla Zer, Alper Akcan, Ibrahim Ali Ozemir, Levent Yeniay, N. Zafer Utkan, Lutfi Dogan, Mutlu Dogan, Mehmet Velidedeoglu, Beyza Ozcinar, Fazilet Erozgen, Abut Kebudi, Kemal Atahan, Vafa Valiyeva, Serdar Yormaz, Ali Sevinc, Cumhur Arici, Atilla Soran, Vahit Ozmen. PD15-01 AXILLARY NODAL RECURRENCE IS RARE IN PATIENTS WITH NODE-POSITIVE BREAST CANCER UNDERGOING SLNB FOLLOWING NEOADJUVANT CHEMOTHERAPY : EARLY RESULTS OF THE NEOSENTITURK-TRIAL/MF-18-03 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-01.
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Cameron, David A., Richard Anderson, Florian Clatot, Isabelle Demeestere, Matteo Lambertini, Scott M. Nelson, and Fedro Peccatori. "Anti-Müllerian hormone (AMH) as a marker of ovarian reserve and premature ovarian insufficiency (POI) in children and women with cancer: A systematic review." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e24057-e24057. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e24057.

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e24057 Background: Female patients undergoing anticancer treatment are at elevated risk of ovarian damage including development of POI. AMH is a key serum biomarker of ovarian reserve. However, its role to identify risk of POI in cancer patients prior to and after treatment is less well understood. Methods: A systematic literature search for AMH in women with cancer was conducted up to 30 August 2020, with formal bias assessment. We aimed at evaluating AMH as a biomarker of ovarian reserve and POI before and after anticancer treatment. Exploratory subgroups were based on age, cancer type and length of follow-up. Results: : Eighty publications (including 7,708 patients) were included in this analysis. All papers reporting AMH before and after treatment reported a large reduction in AMH following treatment, in both adult and paediatric populations. Effect sizes varied depending on the treatment and diagnosis, but ranged from 42% to below the limit of detection, and many reported declines of ≥90%. A majority (25/34, 74%) of studies also reported at least partial recovery of AMH at follow-up. Pre-treatment AMH correlated with post-treatment levels in all studies and younger patient age with higher post-treatment AMH in 21/29 (72%) studies. In 18/32 (58%) publications, oligo/amenorrhea correlated with lower post-treatment AMH. No studies reported correlations between post-treatment AMH and pregnancy, although pregnancy was reported in some patients with low or undetectable AMH. 70% of publications found that within-study variations in treatment (estimated by chemotherapy or radiotherapy type, dosage, duration and/or number of cycles) correlated with AMH reductions and degree of recovery, indicating its potential value as a marker of gonadotoxicity. In women with breast cancer, recovery of AMH was reported in some patients in 10/18 publications; however, AMH levels showed no recovery in many patients receiving alkylating agents or cyclophosphamide-based chemotherapies. In lymphoma, patients receiving ABVD-based regimens had at least partial post-treatment recovery of AMH at follow-up compared with those receiving cyclophosphamide-containing regimens. 16/20 (80%) publications in pediatric cancer patients showed significant reductions in AMH compared with pre-treatment levels or controls. The diagnostic value of post-treatment AMH for POI was supported in 5/5 (100%) studies. AMH levels measured 1–2 years after treatment appeared to be equally reliable at indicating longer-term menstrual outcomes as studies with longer followup. Conclusions: AMH levels were strongly impacted by anticancer treatment, with recovery in some women determined by treatment regimen, age, and pretreatment AMH level. There was evidence for its role in diagnosis of POI, nut further studies are required to clarify its value to assist in patient management.
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Reinert, Tomás, Cristiano P. Souza, Pedro Liedke, Gustavo Werutsky, Laura Testa, Vivian Antunes, Carlos Barrios, et al. "Abstract OT2-22-02: Sequencing of anthracyclines and taxanes during neoadjuvant therapy of locally advanced HER2-negative breast cancer (NEOSAMBA Study/LACOG 0419)." Cancer Research 83, no. 5_Supplement (March 1, 2023): OT2–22–02—OT2–22–02. http://dx.doi.org/10.1158/1538-7445.sabcs22-ot2-22-02.

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Abstract Background: Breast cancer (BC) is the most frequent cancer in women in Brazil, with more than 60,000 cases estimated annually. Forty percent of patients present with stages III and IV and neoadjuvant chemotherapy (NACT) remains the mainstay of treatment for locally advanced breast cancer (LABC). Taxanes usually follow anthracyclines in breast cancer neo/adjuvant treatment, likely because of their later introduction into clinical practice. However, the potential impact of alternative sequencing remains to be studied. A single-center phase II randomized clinical trial conducted in the Brazilian National Cancer Institute showed an improvement in overall survival with taxane-first compared with anthracycline-first sequencing in HER2-negative LABC (Bines J et al, The Oncologist 2020). As a taxane-before-anthracycline sequence carries neither an incremental cost nor increased toxicity, the optimal sequencing of these agents could have significant implications for clinical practice. To confirm this finding, we are currently conducting a multicenter randomized phase III trial comparing a taxane followed by an anthracycline-based regimen with the reverse sequence in the neoadjuvant setting. Trial Design: This randomized, open-label, phase III trial will be conducted in 15 research centers in Brazil. It was approved by the local ethics committee in 2020 and is registered in Clinicatrials.gov with the identifier NCT04540692. Women with HER2-negative LABC are randomized in a 1:1 ratio to anthracycline-before-taxane (AC-T arm) or taxane-before-anthracycline (T-AC arm), stratified by hormone receptor status (positive vs. negative) and axillary lymph node status (N0 vs. N+). The anthracycline-based therapy recommended in this trial is AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) every three weeks for four cycles, whilst the taxane-based therapy is either weekly paclitaxel 80 mg/m2 weekly for 12 weeks, paclitaxel 175 mg/m2 every three weeks, or docetaxel 75-100 mg/m2 every three weeks. The use of carboplatin concomitantly with taxane for triple-negative tumors and dose-dense regimens is allowed following institutional guidelines. Further therapies (surgery, radiotherapy, and endocrine therapy) are performed according to the physicians’ discretion. Tumor samples are collected and stored for translational studies. Eligibility: Inclusion criteria: women ≥18 years of age; histologically confirmed HER2-negative breast cancer (by ASCO/CAP guidelines); stage ≥ IIB (if TNBC) or ≥ III (if HR-positive); PS ECOG 0-2 and adequate organ function. Exclusion criteria: previous use of anti-cancer therapies; bilateral BC and pregnancy. Specific Aims: The primary objective is invasive disease-free survival (iDFS). Secondary objectives include pathological complete response (pCR) rates, overall survival (OS) and safety. Statistical Methods: Considering an unicaudal type I error of 0.05, a type II error of 0.2, and an estimated iDFS of 50% in 5 years in the control arm, a total of 227 evaluable patients should be included per arm to demonstrate a HR of 0.7 favoring the taxane-first arm. Estimating a dropout rate of 10%, 494 patients will need to be included in the study. Present Accrual and Target Accrual: A total of 9 sites of 15 planned are activated. The first patient was enrolled on January 12, 2021, and as of June 24, 2022, a total of 113 patients have been accrued. The target goal of 494 patients is expected to be achieved by 2025 and initial study results will be reported by 2026. Funding: Brazilian Health MInistry, Programa Nacional de Apoio à Atenção Oncológica (PRONON), NUP 25000.183207/2019-50. Acknowledgements: CURA Project, SAS. Citation Format: Tomás Reinert, Cristiano P. Souza, Pedro Liedke, Gustavo Werutsky, Laura Testa, Vivian Antunes, Carlos Barrios, Vivian Vasconcelos, Heloísa Resende, Geraldo Silva Queiroz, Gisah Guilgen, Yeni Nerón, Lilian Arruda Bastos, Sabina Aleixo, Daniel Cubero, Maria Cristina F. Magalhães, Ana Coradazzi, Daniela Galvão B. de Oliveira, João S. Nunes, Rafaela G. Jesus, Gustavo Gössling, José Bines. Sequencing of anthracyclines and taxanes during neoadjuvant therapy of locally advanced HER2-negative breast cancer (NEOSAMBA Study/LACOG 0419) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-22-02.
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Kawano, J., N. Hayashi, A. Yoshida, H. Yagata, and H. Yamauchi. "Pregnancy-Associated Breast Cancer: Chemotherapy During Pregnancy." Annals of Oncology 23 (September 2012): ix133. http://dx.doi.org/10.1016/s0923-7534(20)32937-9.

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Mathelin, Carole, Kadour Annane, Philippe Liegeois, Jean-Pierre Bergerat, and Patrick Dufour. "Chemotherapy for breast cancer during pregnancy." European Journal of Obstetrics & Gynecology and Reproductive Biology 123, no. 2 (December 2005): 260–62. http://dx.doi.org/10.1016/j.ejogrb.2005.05.012.

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25

Acharya, Sandhya C., and Aarati Shah. "Breast cancer during pregnancy." Grande Medical Journal 1, no. 1 (January 3, 2019): 52–54. http://dx.doi.org/10.3126/gmj.v1i1.22414.

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Breast cancer during pregnancy is rare accounting for 1 in around 3000 pregnant women as per the American cancer society. According to hospital-based cancer registry of Nepal, breast cancer accounts for 9.2% of total cancer cases and pregnancy associated breast cancer accounts for 0.15% of the total breast cancer. Though rare, breast cancer is the most common type of cancer found during pregnancy and that too in advanced stage because of the hormonal interplay during pregnancy. Here we present a case of breast cancer during pregnancy which was treated successfully with chemotherapy, surgery, radiation therapy and is on hormonal treatment. Patient is on regular follow up for the last six years without evidence of recurrence of the disease, and the baby has achieved normal developmental milestones though exposed to chemotherapy in utero.
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McArdle, C. S., D. Crawford, E. H. Dykes, K. C. Calman, D. Hole, A. R. Russell, and D. C. Smith. "Adjuvant radiotherapy and chemotherapy in breast cancer." British Journal of Surgery 73, no. 4 (April 1986): 264–66. http://dx.doi.org/10.1002/bjs.1800730407.

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27

Sasidharan, R., and V. Harvey. "Pregnancy and breast cancer." Obstetric Medicine 3, no. 2 (June 2010): 54–58. http://dx.doi.org/10.1258/om.2010.090066.

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Breast cancer is one of the most commonly diagnosed malignancies during pregnancy. Pregnancy-associated breast cancer (PABC) presents a challenging clinical situation. This article reviews the current evidence around the management of PABC and the safety of pregnancy after breast cancer. The trend towards later age at first childbirth has resulted in an increase in the number of breast cancer cases coexistent with pregnancy. The management of breast cancer during pregnancy requires a multidisciplinary team approach. Breast surgery can be safely performed during any trimester of pregnancy. Radiation therapy, if required, must be delayed until after delivery. The majority of patients with PABC require chemotherapy. The timing of delivery in relation to chemotherapy administration should be carefully considered. There is no evidence to date that pregnancy termination influences overall survival for the mother. To date, there is no clear evidence that subsequent pregnancy after breast cancer is associated with worse maternal survival. There is a suggestion that subsequent pregnancy may in fact be associated with an improved survival. However, the available studies are limited by potential biases.
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Kulshrestha, Meeta. "Pregnancy-Associated Breast Cancer." Journal of South Asian Federation of Obstetrics and Gynaecology 3, no. 1 (2011): 1–5. http://dx.doi.org/10.5005/jp-journals-10006-1111.

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ABSTRACT The incidence of pregnancy associated with breast cancer can be expected to increase as maternal age at the time of pregnancy continues to increase. Women diagnosed with breast cancer during pregnancy have similar disease characteristics to age-matched controls. Surgical treatment may be performed as for the nonpregnant women. Radiotherapy and endocrine or antibody treatment should be postponed until after delivery. A multidisciplinary approach is recommended for optimal clinical decision-making. But physicians should be aggressive in the work-up of breast symptoms in the pregnant population to expedite diagnosis. It is generally agreed that therapeutic radiation, if necessary, should be delayed until completion of pregnancy.
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Lenhard, Miriam S., Ingo Bauerfeind, and Michael Untch. "Breast cancer and pregnancy: Challenges of chemotherapy." Critical Reviews in Oncology/Hematology 67, no. 3 (September 2008): 196–203. http://dx.doi.org/10.1016/j.critrevonc.2008.02.007.

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Aristei, Cynthia, Isabella Palumbo, and Elisabetta Perrucci. "The Association of Chemotherapy and Radiotherapy: Breast Cancer." Current Drug Therapy 5, no. 3 (August 1, 2010): 192–201. http://dx.doi.org/10.2174/157488510791561011.

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Wise, J. "Radiotherapy plus chemotherapy is best for breast cancer." BMJ 315, no. 7113 (October 11, 1997): 899–904. http://dx.doi.org/10.1136/bmj.315.7113.899h.

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Colleoni, M., F. Nole’, I. Minchella, C. Noberasco, A. Luini, A. Orecchia, P. Veronesi, S. Zurrida, G. Viale, and A. Goldhirsch. "Pre-operative chemotherapy and radiotherapy in breast cancer." European Journal of Cancer 34, no. 5 (April 1998): 641–45. http://dx.doi.org/10.1016/s0959-8049(97)10091-0.

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33

Tubiana-Mathieu, N., C. Lejeune, P. Bonnier, D. Genet, P. Clavere, J. F. Berdah, F. Delaby, et al. "P66 Inflammatory breast cancer: Chemotherapy and concommittant radiotherapy." European Journal of Cancer 34 (February 1998): S32. http://dx.doi.org/10.1016/s0959-8049(97)89283-0.

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34

Giacalone, Pierre-Ludovic, Francois Laffargue, and Paul B�nos. "Chemotherapy for breast carcinoma during pregnancy." Cancer 86, no. 11 (December 1, 1999): 2266–72. http://dx.doi.org/10.1002/(sici)1097-0142(19991201)86:11<2266::aid-cncr14>3.0.co;2-7.

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35

Litton, Jennifer K., Richard L. Theriault, and Ana M. Gonzalez-Angulo. "Breast Cancer Diagnosis during Pregnancy." Women's Health 5, no. 3 (May 2009): 243–49. http://dx.doi.org/10.2217/whe.09.2.

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Breast cancer diagnosed during pregnancy is a challenging situation for the patient and her medical team. As women are delaying childbirth, the incidence is expected to increase. Most of the data surrounding the diagnosis and treatment of cancer during pregnancy is in case reports and small cohort studies. However, the data continues to expand regarding the safety of systemic treatments during the second and third trimesters for both the mother and the fetus. In this article, the use of diagnostic imaging, procedures, surgery and chemotherapy are reviewed as well as prognosis and future pregnancies after the treatment for breast cancer.
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Nalley, Catlin. "Breast Cancer Patients Treated With Chemotherapy During Pregnancy." Oncology Times 43, S15 (August 5, 2021): 25. http://dx.doi.org/10.1097/01.cot.0000771936.13867.b6.

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Garg, Amit K., and Thomas A. Buchholz. "Influence of Neoadjuvant Chemotherapy on Radiotherapy for Breast Cancer." Annals of Surgical Oncology 22, no. 5 (March 2, 2015): 1434–40. http://dx.doi.org/10.1245/s10434-015-4402-x.

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Arriagada, Rodrigo. "Early breast cancer: Adjuvant chemotherapy or radiotherapy, or both?" Acta Oncologica 45, no. 5 (January 2006): 514–16. http://dx.doi.org/10.1080/02841860600839241.

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39

Héary, Michel, Moise Namer, Michel Moro, Jean-Louis Boublil, and Claude M. Lalanne. "Conservative treatment (chemotherapy/radiotherapy) of locally advanced breast cancer." Cancer 57, no. 9 (May 1, 1986): 1744–49. http://dx.doi.org/10.1002/1097-0142(19860501)57:9<1744::aid-cncr2820570906>3.0.co;2-b.

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40

Harris, Jay R., and Abram Recht. "Sequencing adjuvant chemotherapy and radiotherapy in breast cancer patients." International Journal of Radiation Oncology*Biology*Physics 26, no. 1 (April 1993): 183–85. http://dx.doi.org/10.1016/0360-3016(93)90191-w.

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41

Rounsaville, Mark C. "Primary radiotherapy and chemotherapy for locally advanced breast cancer." International Journal of Radiation Oncology*Biology*Physics 19, no. 4 (October 1990): 1106–7. http://dx.doi.org/10.1016/0360-3016(90)90047-n.

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42

Mkango, Sara B., Nyimvua Shaban, Eunice Mureithi, and Twalib Ngoma. "Dynamics of Breast Cancer under Different Rates of Chemoradiotherapy." Computational and Mathematical Methods in Medicine 2019 (September 11, 2019): 1–12. http://dx.doi.org/10.1155/2019/5216346.

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A type of cancer which originates from the breast tissue is referred to as breast cancer. Globally, it is the most common cause of death in women. Treatments such as radiotherapy, chemotherapy, hormone therapy, immunotherapy, and gene therapy are the main strategies in the fight against breast cancer. The present study aims at investigating the effects of the combined radiotherapy and chemotherapy as a way to treat breast cancer, and different treatment approaches are incorporated into the model. Also, the model is fitted to data on patients with breast cancer in Tanzania. We determine new treatment strategies, and finally, we show that when sufficient amount of chemotherapy and radiotherapy with a low decay rate is used, the drug will be significantly more effective in combating the disease while health cells remain above the threshold.
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43

Gold, H. T., and H. T. Do. "Impact of timeliness of breast radiotherapy on health outcomes in early breast cancer." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 6591. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.6591.

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6591 Background: The objective of this study is to understand the impact of timely radiotherapy on disease-free survival (DFS) in early breast cancer patients ages 65 and above. Methods: The study population is women diagnosed from 1991–1999 in the linked SEER-Medicare database who underwent breast-conserving surgery and radiotherapy within 6 months of diagnosis. Median followup varies from 4 years for ductal carcinoma in situ (DCIS)(n=1,185) to 5 years for Stage 1 disease (n=7,481), and ranges from 0–11 years. Descriptive and proportional hazards analysis of this longitudinal cohort were conducted. Covariates include age, race, poverty, marital status, comorbidity, rurality, radiation completion and delay, elapsed time since diagnosis, comedo necrosis histology (DCIS only), and chemotherapy receipt (Stage 1 only). Subjects were censored at end of followup (including enrolling in Medicare managed care from Medicare fee-for-service) or death. Treatment delay is defined as radiotherapy beginning 8+ weeks post-surgery without chemotherapy or 4+ weeks after chemotherapy ends; other definitions also were explored. Radiotherapy is considered complete if the patient received greater than 16/22 of expected treatments, based on scientific literature. Results: DFS is negatively associated with radiation delay (OR=1.24, p=0.003 for Stage 1; OR=1.40, p=0.054 for DCIS) and Klabunde's inpatient comorbidity index (OR=1.32, p=0.004 for Stage 1; OR=1.66, p=0.065 for DCIS). Additional analyses suggest that a longer delay of 12+ weeks post-surgery (16+ weeks post-chemotherapy) further reduces DFS (OR=4.66, p<0.0001 for Stage 1; OR=12.4, p<0.0001 for DCIS). Non-white women with Stage 1 disease are more likely to delay radiotherapy (p<0.0001), but are not more likely to have worse outcomes (p>0.3). Conclusions: Delayed initiation of radiation therapy is associated with decreased DFS following radiotherapy for early breast cancer and DCIS. Non-white race is associated with delay, but not reduced DFS. Programs targeting referring physicians and patients should be developed to promote timely receipt of radiotherapy by early breast cancer patients, thereby reducing the risk of adverse health outcomes. No significant financial relationships to disclose.
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Jobsen, Jan J., Job van der Palen, Mariël Brinkhuis, Francisca Ong, and Henk Struikmans. "Sequence of Radiotherapy and Chemotherapy in Breast Cancer After Breast-Conserving Surgery." International Journal of Radiation Oncology*Biology*Physics 82, no. 5 (April 2012): e811-e817. http://dx.doi.org/10.1016/j.ijrobp.2011.11.020.

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45

Bellon, J. R. "Sequence of Radiotherapy and Chemotherapy in Breast Cancer After Breast-Conserving Surgery." Breast Diseases: A Year Book Quarterly 23, no. 4 (January 2012): 388–90. http://dx.doi.org/10.1016/j.breastdis.2012.10.015.

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46

Cameron, J. "Radiographer review clinics: breast cancer." Journal of Radiotherapy in Practice 4, no. 1 (June 2004): 33–38. http://dx.doi.org/10.1017/s1460396904000068.

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Acute skin reactions are expected in patients receiving radical radiotherapy to the breast. Side effects of other adjuvant treatments such as chemotherapy and hormonal therapy can further impact upon patients' well being. As a result these patients are routinely monitored throughout their radiotherapy treatment at a review clinic. Previously the domain of doctors, radiographers are expanding their existing role and becoming more involved in review clinics.This paper highlights the key side effects reported by actual patients from their adjuvant treatment and strategies to alleviate these side effects. It also reflects upon the experience, both positive and negative, of undertaking clinical review and role expansion in general.
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Kerr, Julia R. "Neonatal Effects of Breast Cancer Chemotherapy Administered During Pregnancy." Pharmacotherapy 25, no. 3 (March 2005): 438–41. http://dx.doi.org/10.1592/phco.25.3.438.61590.

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48

Dabic, B., S. Gambiroza, G. Malcic-Kecman, and P. Dasic. "PR71 Chemotherapy for breast cancer during pregnancy: case report." Breast 21 (November 2012): S23. http://dx.doi.org/10.1016/s0960-9776(12)70078-4.

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49

Hensley, M. "Fertility and pregnancy after adjuvant chemotherapy for breast cancer." Critical Reviews in Oncology/Hematology 28, no. 2 (August 1998): 121–28. http://dx.doi.org/10.1016/s1040-8428(98)00013-4.

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50

Monteiro, Denise Leite Maia, Alexandre José Baptista Trajano, Daniela Contage Siccardi Menezes, Norma Luiza Machado Silveira, Alessandra Caputo Magalhães, Fatima Regina Dias de Miranda, and Barbara Caldas. "Breast cancer during pregnancy and chemotherapy: a systematic review." Revista da Associação Médica Brasileira (English Edition) 59, no. 2 (January 2013): 174–80. http://dx.doi.org/10.1016/s2255-4823(13)70452-1.

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