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Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 6958952, 5 pages https://doi.org/10.1155/2019/6958952 Case Report Synchronous Ovarian and Breast Cancers with a Novel Variant in BRCA2 Gene: A Case Report 1,2 2 3 Néstor Llinás-Quintero , Eduardo Cabrera-Florez, Gustavo Mendoza-Fandiño, 4 5 2 Gustavo Matute-Turizo, Elsa M. Vasquez-Trespalacios , and Luis J. Gallón-Villegas Breast Surgery Fellowship Program, School of Medicine, CES University, Medellín, Colombia School of Medicine, CES University, Medellín, Colombia Departament of Public Health, School of Medicine, CES University, Medellín, Colombia Pathology and Cytology Laboratory LLC (LAPACI), Medellín, Colombia Epidemiology Department, School of Medicine, CES University, Medellín, Colombia Correspondence should be addressed to Néstor Llinás-Quintero; email@example.com Received 2 March 2018; Revised 10 September 2018; Accepted 9 December 2018; Published 6 January 2019 Academic Editor: Su Ming Tan Copyright © 2019 Néstor Llinás-Quintero et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We report a case of a 52-year-old female with a family history of pancreatic and colon cancers who presented with a right breast mass positive for high-grade medullar carcinoma with triple-negative biomolecular proﬁle. Further workup was performed ﬁnding a left ovarian mass. The patient underwent laparotomy performing optimal cytoreduction on bilateral ovarian tumors; the pathology and immunohistochemistry conﬁrmed bilateral ovary adenocarcinoma with positive peritoneal malignancy. Due to her synchronic breast and ovarian cancers, a genetic proﬁle was performed detecting a new pathogenic variant in the BRCA2 gene: c.3606_3607del (p.Ser1203Cysfs). She was given chemotherapy with carboplatin and paclitaxel obtaining complete clinical response. Regarding her breast cancer, she had a right modiﬁed radical mastectomy and prophylactic left mastectomy obtaining complete clinical response. This case presents with an unusual subtype and diﬃcult histologic diagnosis of a synchronic medullar breast cancer and ovary carcinoma associated with a new mutation of the BRCA2 gene. 1. Case Report We evaluated metastasis by chest X-rays and bone scintigraphy; no evidence of metastasis was identiﬁed. Abdominal ultrasound did not report liver lesions. A left A 52-year-old patient presented with a tumor on her right ovary lesion was identiﬁed measuring 105 × 101 × 80 mm. breast. Routine mammography classiﬁed it as BIRADS-0. A The patient underwent exploratory laparotomy, which mammary ultrasound conﬁrmed a complex cystic lesion in allowed the identiﬁcation and resection of bilateral ovarian the upper quadrants of the right breast. Histopathological analysis of a biopsy of the tumor showed a poorly diﬀeren- tumors. During the laparoscopic resection, analysis of the left ovary indicated an epithelial malignant tumor, consistent tiated carcinoma with necrosis. An incisional biopsy of the with breast cancer metastasis. Bilateral ovarian involvement breast tumor was performed and histopathology analysis by poorly diﬀerentiated adenocarcinoma was reported. Peri- reported it as a nuclear grade-3 medullary carcinoma. Pathol- toneal cavity cytology identiﬁed additional malignancies, ogy and immunohistochemistry of the lesion (60 × 40 mm) revealed an estrogen receptor negative (ER-), progesterone which by immunohistochemical studies were positive for the expression of WT1 and CA125 proteins suggesting an receptor negative (PR-), HER2 negative (HER2-), and ovarian origin. The ovarian lesion was classiﬁed as serous Ki67 index of 20% mass (Figure 1), which led to the cystadenocarcinoma. The patient underwent ovarian cancer diagnosis of adenocarcinoma stage IIB (pT3N0M0) of the staging surgery; uterine surgical pathology, remnant annexes, right breast. 2 Case Reports in Oncological Medicine (a) (b) (c) (d) (e) (f) Figure 1: Immunohistochemical analysis of the breast lesion. (a) H&E 200x: central necrosis is observed, peripheral neoplastic cells with eosinophilic cytoplasm, large nuclei, prominent nucleoli, atypical mitosis, and mononuclear inﬁltrates. Representative micrographs (at 400x) are shown for immunohistochemical analysis of (b) leukocyte common antigen (LCA), showing positive expression in peritumoral lymphocytes. (c) Ki67 expression is detected in 60% of cancer cells; lack of expression of (d) estrogen receptor (ER), (e) progesterone receptor (PR), and (f) HER2. appendix, and omentum were negative for malignancy, 2. Discussion obturator nodes were negative (0/11), and diaphragmatic cytology and parietocolic leakage were also negative. The Triple-negative breast cancer (TNBC) and BRCA1/2-mu- ﬁnal diagnosis was high-risk synchronous cancer, stage IIB tated breast cancers have been previously reported to exhibit triple-negative breast cancer, and stage IIIA ovarian cancer. sensitivity to platinum-based chemotherapy . Thus, estab- The patient received adjuvant systemic therapy to treat lishing BRACA1/2 status may be useful to provide a tailored the ovarian cancer and neoadjuvant therapy to treat the chemotherapeutic regimen. The identiﬁcation of patients at locally advanced breast cancer. The regimen was carboplatin risk of being a carrier of BRCA1/2 mutation is relevant to AUC5+paclitaxel 175 mg/m day, every 21 days × 6 cycles, hereditary cancer. BRCA1/2 mutation carriers are at high well tolerated, and exhibited complete clinical response. risk of breast cancer (RR > 10), similar to that observed in Genetic testing for BRCA1 or BRCA2 mutations (Myriad patients with a history of chest radiotherapy (usually lym- phatic cancer, before 30 years old) [2, 3], breast surgery, Genetics) reported a BRCA2 deleterious mutation: c.3606_ 3607del (p.Ser1203Cysfs) (Figure 2). The patient underwent systemic therapy, and other prophylactic interventions . bilateral mastectomy and axillary lymph node dissection. Furthermore, when designing the strategy and therapeu- The ﬁnal surgical pathology report indicated no residual tic approach for BRCA1/2 mutation carriers, the possibility disease, including 14 axillary ganglia, and a complete patho- of encountering synchronous and/or metachronous disease logical response (ypT0N0M0). Coadjuvant radiotherapy was must be taken into consideration. However, when diagnosing of 5000 cGy. Clinical follow-up after 33 months since diagno- synchronous disease, establishing whether it is a primary sis revealed no evidence of recurrent lesions and the patient ovarian cancer or a breast cancer metastasis to the ovary reported her life quality as good. may be challenging to determine. The additional possibility Regarding the family history, a sister presents the same of it being a metastatic ovarian cancer to the breast is seldom mutation in BRCA2: c.3606_3607del (p.Ser1203Cysfs). To found in the literature, and up to December 2015, only 110 our knowledge, their mother died with pancreatic cancer cases have been reported [5, 6]. While criteria used to identify and the father was diagnosed with colon cancer. Family metastatic carcinomas—and diﬀerentiate them from primary members are currently undergoing additional genetic tests. tumors—are mainly based on clinicopathologic ﬁndings, loss 6503 del TT 6252 ins G 6076 del GTTA 5844 del5 3606-3607 del (Ser1203Cys)fs 3034 del ACAA W31X Case Reports in Oncological Medicine 3 50 kb hg38 32,310,000 32,330,000 32,350,000 32,370,000 32,390,000 32,410,000 BRCA2 Exons 3 10 11 27 Figure 2: BRCA2 pathogenic variant: c.3606_3607del (p.Ser1203Cysfs). of heterozygosity (LOH) and mutational analysis may a speciﬁc standard of care protocol for the treatment of med- provide useful additional information, since prognosis and ullary carcinoma. Nonetheless, the NCCN provides clinical therapy of those two entities are diﬀerent . Furthermore, guidelines for the treatment of medullary carcinomas, which breast cancer metastasis to the ovaries with a prevalence from are similar to those established for other inﬁltrating ductal 10 to 30% is associated with BRCA1/2 mutation carriers, carcinomas of comparable size, grade, and LN status. which have worse prognosis, and is usually diagnosed during Additionally, medullary breast cancer has also been shown autopsy, prophylactic or therapeutic oophorectomies, and as to have a comparable metastatic ability to that of other incidental ﬁndings during routine surgery . To date, met- high-grade carcinomas. Therefore, our patient was treated astatic breast cancer is generally identiﬁed histologically by with standard-of-care combination therapy for serous ovar- the positive expression of gross cystic disease ﬂuid protein ian cancer (carboplatin+paclitaxel), as well as neoadjuvant 15 (GCDFP15), mammaglobin, and GATA3 and by the lack therapy for BRCA2 mutation carrier TNBC patients of expression of PAX8, CA125, and WT1. However, this is [13, 14]. While there is currently no standard of care in the not always the case, since within the TNBC, the basal subtype neoadjuvant setting for TNBC, and even to a lesser extent exhibits low expression of GCDFP15 (11.9%) and mamma- for BRCA1/2 mutation carrier breast cancer patients, several studies have reported the sensitivity of these tumors to globin (21.4%) . Positive expression of CA125 and WT1 in metastatic breast cancer has also been reported . platinum-based chemotherapy. The CALGB/Alliance 40603 Contrary to metastatic breast cancer, serous ovarian carci- and GeparSixto studies reported a pathological complete noma shows positive expression of PAX8, CA125, and response (pCR) and an improved disease-free survival WT1 and lacks expression of (GCDFP15), mammaglobin, (DSF) for TNBC patients receiving carboplatin + standard of care in the neoadjuvant setting. Analysis of BRCA1/2 and GATA3. On the other hand, primary endometrioid ovar- ian cancer is usually identiﬁed by positive expression of CK7, mutation carriers in those same studies showed no signiﬁcant estrogen receptor (ER), CA125, and PAX8, while lacking eﬀect in pCR (52% and 4.7%, respectively), and while DFS expression of CK20, CEA, and CDX2 [9–12]. was 85%, a greater toxicity was also reported for these Our patient was diagnosed with high-risk synchronous patients [15, 16]. Preliminary results from a third phase II study reported that the addition of nab-paclitaxel to carbo- cancer: stage IIB TNBC and stage IIIA ovarian cancer. Immunohistochemical analysis in the ovarian tissue showed platin led to a pCR of 53% . Anthracycline-based therapy positive expression of CA125 and WT1. Because medullary is considerably toxic, thus—aiming to reduce toxicity—other carcinoma is uncommon, diﬃcult to diagnose, and has anthracycline-free regimens have also been studied. A study signiﬁcant interobserver variability, the National Compre- of 190 stage I-III TNBC revealed that patients (including BRCA1/2 germline mutation carriers) were treated in the hensive Care Network (NCCN) currently does not include 4 Case Reports in Oncological Medicine neoadjuvant setting with carboplatin (AUC 6)+docetaxel Conflicts of Interest (75 mg/m ), every 21 days, for 6 cycles. In that study, 16% The authors declare that they have no conﬂicts of interest. of the patients were BRCA1/2 germline mutation carriers and exhibited a pCR of 59%, comparable to that observed Acknowledgments by adding carboplatin to the anthracycline-taxane regimen . Similarly, the phase II BSI-201 study (Telli et al.) Authors warmly thank CES University and Clinica Vida for showed that BRCA1/2 germline mutation carrier TNBC their support to this project. patients exhibited a pCR of 56% when treated with gemci- tabine, carboplatin, and iniparib (GCI), comparable to that References reported for TNBC patients receiving carboplatin+pacli- taxel in the neoadjuvant setting [19–21]. The I-SPY2 study  A. Dilawari, J. Cangiarella, J. Smith, A. Huang, A. Downey, and found a pCR of 52% in TNBC patients treated with F. 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