Metachronous Breast Research Articles

Dual-isocentric volumetric modulated arc therapy in synchronous bilateral breast cancer irradiation: A dosimetric study

Introduction: In synchronous or metachronous breast cancer, bilateral breast irradiation is one of the major problems of radiation oncology. In this study, dosimetric radiation treatment of bilateral breast cancer (BBC) in two cases of synchronous bilateral mammary cancer will be discussed. In this study, a conformal radiotherapy (RT) plan for bilateral breast irradiation is discussed over two cases with synchronous BBC (sBBC). Materials and Methods: Two cases with sBBC requiring irradiation of dual breasts and regional nodal areas were chosen. Data from bilateral breast irradiation studies were used rather than dose recommendations used in unilateral breast irradiation for organs at risks. The dual-isocentric four-half-arc option was utilized in volumetric-modulated arc therapy (VMAT) plans. The dynamic sliding window method with fixed gantry angle was utilized in intensity-modulated radiation therapy (IMRT) plans. Results: Both IMRT and VMAT plans were chosen for the patients. D95% of the planning target volume supplied the desired dose prescription in the VMAT and IMRT plans of Case 1 and in the IMRT plan of Case 2, whereas the VMAT plan of Case 2 did not achieve the desired dose prescription at the target. The conformity index (CI) was the ideal plan in Case 1's VMAT plan, while Case 2's VMAT plan deviated greatly in terms of the CI value. The VMAT and IMRT plans of Case 1 and the IMRT plan of Case 2 were considered to be more homogeneous plans than the value closest to zero in terms of homogeneity index, whereas the VMAT plan of Case 2 was not considered homogeneous. Conclusion: It is recommended that in sBBC RT confined to breast only dual isometric, four half arc VMAT is an appropriate plan.

Metachronous breast neoplasms: squamous cell carcinoma and lobular carcinoma in situ within a fibroadenoma

Breast squamous cell carcinoma are rare, occurring in less than 0.1% of all breast carcinomas. This report describes the oncological conduct performed on a patient with a triple negative squamous cell carcinoma in the upper outer quadrant of the right breast. The same patient presented a lobular carcinoma in situ within a fibroadenoma of the contralateral breast, during the follow up period. The association of these two diseases in the same patient has not yet been described in the literature.

Serum tumor markers and positron emission tomography-computed tomography scan as post-breast cancer treatment surveillance

Background: Post-operative surveillance is an important aspect in managing breast cancers. The primary aim is to allow early detection of metachronous breast cancers. However, post-operative breast cancer surveillance has not been standardized. Mammography has been the only evidence-based imaging modality for detecting metachronous breast cancers. The value of regular monitoring with serum carcinoembryonic antigen (CEA) and CA 15-3 has been controversial. The aim of this study is to evaluate the efficacy of using tumor markers as a surveillance tool in post-operative patients. Methods: This is a retrospective review of all post-breast cancer surgery patients monitored with tumor markers from 2005–2010. Correlation between tumor markers and subsequent detection of metachronous breast cancer was evaluated. Long-term survival data was analyzed. Results: Six hundred and forty-nine patients underwent positron emission tomography-computed tomography (PET-CT) scan, 250 patients had regular tumor markers monitoring. By using 5 ng/mL as cutoff for CEA, and 23 U/mL for CA 15.3, elevated levels are associated with development of metachronous breast cancer (P=0.004 and P Conclusions: Elevated serum CEA and CA 15-3 is associated with metachronous breast cancer and is associated with adverse long-term survival outcome.

Do all BRCA1/2 carriers with breast cancer benefit from bilateral mastectomy?

Surgical management of hereditary breast cancer is influenced by several variables pertaining tumor biology as well as patients’ physical and psychological characteristics. The prevalence of BRCA1/2 mutations among breast cancer patients is low, but many carriers are not diagnosed according current criteria of access to genetic testing. This is becoming even more relevant as specific drugs for carriers have now been included in the armamentarium of medical oncologists. Indeed, the whole therapeutic strategy, including pros and cons of radiotherapy, is influenced by BRCA1/2 status. Although no major differences have been reported between the outcome of BRCA1/2 negative vs. BRCA1/2 positive patients, the latter carry a substantially higher cumulative risk of metachronous breast and ovarian cancers. It is then mandatory that the complex interplay between clinical, biological and treatment variables be fully taken into account when cancer develops in these women.

Morphometric Characteristics and Features of Metachronous Breast Cancer

An important morphological criterion for the development of the degree of malignancy of breast cancer is the change in the structure of cell nuclei. At the same time, both the morphometric parameters of metachronous breast cancer and their connection with the molecular biological characteristics of these tumors are currently unknown.
 The objective of the research was to identify metachronous malignant disease in the patients with breast cancer.
 Materials and methods. The study is based on a retrospective analysis of tumors in 63 patients with breast cancer, who developed uterine cancer or ovarian cancer within 5 years after diagnosis of breast cancer. All the patients received treatment at the Ivano-Frankivsk Regional Clinical Oncology Center. The criterion for selecting patients in the study was the presence of gynecologic cancer after the treatment of breast cancer. The age of patients with breast cancer involved in the study ranged from 24 to 83 years, averaging 56.8±1.5 years.
 Results and discussion. The maximum values ​​of the perimeter, radius, and area of ​​cell nuclei (19.21±0.7, 3.05±0.4 and 36.3±0.9, respectively) were observed in tumors of the patients with metachronous breast cancer. The improvement of the perimeter, radius, and area of ​​tumor cell nuclei in the patients with metachronous breast cancer was associated with an increase in the size of the tumors and the presence of metastases in regional lymph nodes.
 Conclusions. The morphometric sign of the high risk of developing metachronous breast cancer is the increase in the perimeter, radius, and cell nucleus area on the background of increased proliferative activity of low-grade cancer in the presence of large tumors and metastases in regional lymph nodes.

Abstract P4-09-07: Higher risk of metachronous contralateral breast cancer in patients with invasive lobular breast cancer

Abstract Background: Risk of metachronous contralateral breast cancer (CBC) is an important health issue in primary breast cancer (PBC) survivors. Individualized CBC risk prediction can help identify patients at high or low risk who may or may not benefit from additional surveillance and treatment. For lobular PBC, inconsistent results have been reported on an association with increased risk of CBC. We investigated CBC risk in lobular versus ductal PBC using a large nationwide dataset and taking into account age at PBC and (neo-)adjuvant systemic therapy effects. Patients and Methods: We selected women diagnosed between 2003 and 2010 with early invasive lobular, lobular mixed with other types, or ductal PBC from the Netherlands Cancer Registry. Categorical and continuous characteristics between the 3 groups were compared using the chi-square statistics and the Kruskal-Wallis test, respectively. Competing risk analyses were applied to determine CBC incidence. Multivariable subdistribution hazard ratios (SHRs) were adjusted for primary tumor stage, age at PBC diagnosis, radiotherapy, (neo-)adjuvant chemotherapy and endocrine therapy. Results: We selected 74,373 women aged >18 years with lobular (n=8,903), lobular mixed (n=3,512), and ductal (n=62,230) PBC. Women with lobular PBC were older at diagnosis than women with lobular mixed or ductal PBC (61 vs. 58 vs. 58 years, respectively), more often had ER-positive PBC (95.7% vs. 94.1% vs. 79.6%) and were more often systemically treated with only endocrine therapy (30.7% vs. 24.9% vs. 19.7%), while less often treated with only chemotherapy (4.2% vs. 5.3% vs. 15.4%). Ten-year cumulative CBC incidences in women with lobular, lobular mixed or ductal PBC were 3.2%, 3.6% and 2.8% when treated with systemic therapy (chemotherapy and/or endocrine therapy) and 6.6%, 7.7% and 5.6% without systemic therapy, respectively. Multivariable SHRs were 1.19 (95% CI: 1.05-1.34) for lobular and 1.39 (95% CI: 1.17-1.65) for lobular mixed versus ductal PBC; for women <50 years, risk differences were larger: 1.60 (95% CI: 1.26-2.05) and 1.43 (95% CI: 1.00-2.06), respectively. Conclusion: Lobular histology and lobular mixed histology are independent risk factors for CBC development, and should be considered as prognostic factors when refining CBC risk prediction models. Citation Format: Akdeniz D, Kramer I, van Deurzen CH, Schaapveld M, Westenend PJ, Voogd AC, Jager A, Steyerberg EW, Sleijfer S, Schmidt MK, Hooning MJ. Higher risk of metachronous contralateral breast cancer in patients with invasive lobular breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-09-07.

A case of locally advanced adenosquamous carcinoma of the cecum with long-term survival.

A 63-year-old woman was admitted to our hospital with a right lower abdominal mass and general fatigue. Preoperative examination suggested a large ovarian tumor or cecal carcinoma. However, her intraoperative diagnosis was colon cancer; we therefore performed an ileocecal resection with oophorectomy. The tumor was pathologically diagnosed as adenosquamous carcinoma T4bN1M-stage IIIa. We administrated CapeOX adjuvant chemotherapy for 6 months. Adenosquamous carcinoma is extremely rare, at around 0.1% of all colorectal cancers, and usually has a poor prognosis. The patient is still alive without recurrence after 84 post-operative months, even with later developments of metachronous early colorectal cancer and breast cancer. We herein report a rare case of cecal ASC with good prognosis.

Bilateral Metachronous Breast Cancer

Bilateral Metachronous Breast Cancer

Metachronous or synchronous male breast and prostate cancers a duality to lookout for.

Introduction: Breast cancer is well known as the stereotypical women's cancer, and prostate cancer represents the well-known stereotypical male counterpart. While prostate cancer carries the potential to metastasize to the breast, the synchronous or metachronous co-occurrence of primary breast and primary prostate cancers is quite unusual. Prostate cancer in men of African descent may have its own behavior with regards to its relationship with male breast cancer. Case presentation: Case 1: A 64 year old male presented to Chris Hani Baragwanath Hospital (CHBAH) with a 2 years history of a painless left breast lump. A core biopsy was confirmed breast carcinoma. Tamoxifen was started but, due to disease progression, he underwent left modified radical mastectomy followed by chemotherapy. Prostate biopsy was done for raised Prostate Specific Antigen (PSA) and suspicious prostate on digital rectal examination. A prostatic adenocarcinoma was subsequently diagnosed with bone metastasis on bone scan. He was started on Androgen deprivation therapy and followed up every 3 months. Case 2: A 68 year old male presented to CHBAH with a 1 year history of a painless right breast lump. A core biopsy confirmed breast cancer. Tamoxifen was started, followed by right modified radical mastectomy and chemotherapy for disease progression. A raised PSA and suspicious prostate on digital rectal examination prompted a prostate biopsy revealing a prostatic adenocarcinoma. Bone scan was negative for metastasis. He is currently on 3 monthly Androgen deprivation therapy and awaiting radiation. Conclusion: This clinical practice article not only presents this exceptionally rare duality but highlights that both cancers can coexist either as sporadic conditions, or as a result of genetic mutations. Thus, we suggest that men with prostate cancer be screened clinically, biochemically and genetically for breast cancer and vice versa.

Abstract 3440: Genomic evolution of synchronous and metachronous breast cancer metastasis revealed from a prospective clinical trial

Abstract Background: Tumor progression is an evolutionary process associated with the accumulation of somatic genomic alterations. Even though metastasis is a fundamental process and a challenging issue for the progress in targeted treatment, the molecular drivers of cancer metastasis remains poorly understood. Despite the advance in high throughput sequencing and the characterization of hundreds of breast tumor genomes, it is still unclear whether cancer genomes evolve by neutral processes or whether genetic alterations that favorable tumor progression are selected under pressures of cancer therapy or both. To gain insights into the molecular processes driving breast cancer metastasis and to identify targetable genetic events associated with early and late stages of the disease, we studied the mutational profiles of a series of paired primary breast tumors and subsequent metastases collected as part of the ESOPE clinical Trial. Methods: Matched primary breast tumors, first metastases and germline DNAs were obtained from 31 patients, divided in 10 therapy-naïve synchronous primary cancers and metastases and 21 metachronous primary tumors and metastases that undergone first line adjuvant treatments. On Illumina platform, WES was performed and three variant callers were used in parallel to predicted variations. After annotation, variants with low 1000Genome frequency and absent in germline samples, were validated by IGV visualization and then considered as somatic variants. To identify significantly mutated genes, we used the Mutation Significance (MutSigCV) tool and the Cancer Gene Census list of relevant genes. Analysis of mutational process signatures was also performed though DeconstructSigs R packages. Results: Synchronous and metachronous metastases globally exhibited similar mutation rates, however a significant difference was observed in the number of accumulated private mutations in both types of metastases. With few exceptions, our data indicate that the genomic profiles of metastases mainly diverge late in breast cancer progression, with relatively few private mutations in the primary tumors. In contrast, an increase of somatic variants was found in the metachronous metastases as compared to their primary tumors of origin. Most of driver mutations were shared by primary tumors and metastases but additional drivers were highlighted in the metastatic lesions, such as variants of PIK3CA, IGF1R, CDH1, NF1 as well as ESR1. Moreover, recurrent mutated genes were also identified in metastases that have not been previously described (FDR<0.1). Analyses of mutational signatures revealed a shift towards APOBEC, POLE, MMR and HR activity. In conclusion, synchronous and metachronous breast cancers differ in their genomic evolution and the characterization of driver mutations in metastases might open new avenues for novel therapeutic strategies in metastatic breast cancer. Citation Format: Keltouma Driouch, Zakia Tariq, Sylvain Baulande, Virginie Raynal, Virginie Bernard, Francois-Clement Bidard, Vanessa Benhamo, Ivan Bieche, Brigitte Sigal, Rosette Lidereau, Paul Cottu. Genomic evolution of synchronous and metachronous breast cancer metastasis revealed from a prospective clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3440.

Abstract P3-10-13: Bilateral breast cancer in China: A 10-year single-center retrospective study

Abstract BACKGROUD: Women with unilateral breast cancer are at increased risk for developing contralateral disease. The objective of the single-center retrospective study was to evaluate the incidence of bilateral breast cancer (BBC) and to analyze the clinicopathological characteristics for BBC in China. METHODS: We retrospectively reviewed the electronic medical records of 3924 female patients with breast cancer consecutively treated at the department of Breast Oncology in the Peking University Cancer Hospital between 2006 and 2016. BBC was categorized as synchronous (within 6 months) or metachronous bilateral breast cancer (after 6 months of a first tumor). Patients with BBC were identified according to the criteria described by Chaudary et al. Patients with stage IV first breast cancer, and those who were found to have distant metastases between the first and second primary breast cancer were excluded. Analyses of demographic, clinicopathologic, and treatment characteristics were done between sBBC and mBBC. RESULTS: The incidence of BBC in our population was 3.2% (127 of 3924). Of those, 2.5 % ( 99 of 3924) were metachronous bilateral breast cancer ( mBBC ), and 0.71 % (28 of 3924) were synchronous bilateral breast cancer ( sBBC ). The overall median age of the patients at first diagnosis was 45 years (range, 27-81 years). The age of onset of the first mBBC was significantly younger than that of sBBC ( p = 0.027). In mBBC subgroups, the median time interval between first and second tumors was 68 months (range, 7-342 months), and 80.8% of the second tumor were diagnosed within 10 years of the diagnosis of the first tumor. A positive family history of breast cancer was found in 25% of sBBC and 9.1% of mBBC ( p = 0.025). In ER-negative first tumor of mBBC, 56.1% of the second tumor were ER-positive. Mastectomy was the commonest surgery performed in these patients. CONCLUSIONS: Our results confirmed the necessity of screening contralateral breast at the diagnosis of unilateral breast cancer and following-up for Chinese patients with breast cancer. Citation Format: Li H, Jiang H, Zhang R, Shao B, Yan Y, Ran R, Di L. Bilateral breast cancer in China: A 10-year single-center retrospective study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-13.

Long-term survival in a patient with bilateral metachronous triple negative breast cancer: A case report and literature review

The incidence of bilateral metachronous breast cancer is rare in our environment. We report the rare case of a 44-year-old woman who has survived for 12 years after she was first diagnosed with stage 3B medullary right breast cancer. She had a positive family history of breast cancer in her paternal grandmother. She was treated with mastectomy and axillary clearance, six cycles of combination chemotherapy and external beam radiotherapy. She was also placed on tamoxifen. She developed a second primary breast cancer in the contralateral breast; triple negative, 10 years after her first diagnosis. She was treated with modified radical mastectomy and six cycles of Docetaxel with excellent response. She completed her chemotherapy about 2 years ago and has been on follow-up with no evidence of loco-regional recurrence.

Clinicopathological Profile and Treatment Outcomes of Bilateral Breast Cancer: A Study from Tertiary Cancer Center in South India

Abstract Background: Bilateral breast cancer (BBC) is a rare clinical entity with limited data regarding clinicopathological aspects and treatment guidelines. Materials and Methods: This was an observational study of patients diagnosed with BBC from August 2012 to July 2014. Synchronous breast cancers (SBCs) was defined as two tumors diagnosed within an interval of 6 months and metachronous breast cancer (MBC) as second cancer diagnosed after 6 months. Results: Out of 750 breast cancer patients seen during a 2-year period, 35 had BBC. Ten patients were diagnosed as SBC whereas 25 patients as MBC. Among patients with MBC, the average time for development of contralateral breast cancer was 5 years. In 8 patients, the contralateral breast cancer was detected mammography whereas rest 27 patients were detected by clinical breast examination. At a median follow-up of 24 months, 23 (66%) patients were disease free, 9 (26%) patients had disease relapse, and 3 (8%) patients succumbed to the progressive disease. Conclusions: Every patient with breast cancer should be regularly followed up with clinical breast examination at a more frequent interval. The role of frequent clinical breast examination appears more than mammography especially beyond 5 years for early detection of contralateral breast cancer.

Synchronous and metachronous breast cancer in Ukraine.

This study aims to describe the current state of multiple primary malignant neoplasms (MPMNs) breast cancer patients management, evaluate the predictive impact of different factors, optimise approaches to diagnosis and treatment of these patients and improve their life quality. The study included 2,032 patients who received special treatment at the Department of Breast Tumours and it Reconstructive Surgery of the National Cancer Institute from 2008 to 2015 within an open randomized controlled trial. The sample included 195 patients with synchronous cancer or metachronous breast cancer. A more aggressive course of breast cancer is observed in patients exposed to radiation from the Chornobyl accident. The clinical course of disease in patients with synchronous breast cancer is worse and prognostically unfavourable comparing to metachronous one. The influence on clinical course of disease of primary localization, type of settlement, blood group and Rh factor, type of special treatment, and age in patients with synchronous and metachronous cancer was not statistically proven. The impact of operative intervention scope in patients with synchronous and metachronous breast cancer was statistically proven, i.e. the course of the underlying disease in patients who underwent mastectomy is worse comparing to patients who underwent conservative surgery. Plastic and reconstructive surgery in patients with synchronous cancer was statistically proven in this study as reasonable. The influence of local recurrence rates on overall survival in patients with synchronous cancer was proven. However, the influence of local recurrence rates in patients with metachronous cancer was not statistically proven. There should be paid a great attention to synchronous and metachronous breast cancer patients in order to find and provide the best options of their management. This is crucial to continue researches in this field of oncology.

Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan

The hereditary breast and ovarian cancer (HBOC) registration system of Japan was established by the Japanese HBOC Consortium. The first trial was registered in 2015 in four institutions to which some registration committee members belonged. We analyzed the information of 830 Japanese pedigrees, who underwent BRCA1/2 genetic testing, including mutation carriers with BRCA1 (N = 127) and BRCA2 (N = 115), and their families. The mutation-positive rate was 19.7%. Variants of uncertain significance were found in 6.5% of all individuals subjected to genetic testing for BRCA1/2. Compared to the United States, Japan had a higher mutation-positive rate in most categories, except for the groups with male breast cancer. Among the intrinsic subtypes of BRCA1-associated breast cancers, 75.8% were triple-negative. The incidence rate of contralateral breast cancer in BRCA1/2 mutation carriers was 0.99%/year. Among 240 mutation carriers, 26 and 62 patients underwent risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), respectively; the respective frequencies of occult cancer were 7.1 and 3.2%. Metachronous breast cancer after RRM or peritoneal cancer after RRSO was not observed during the follow-up period. The nationwide registration system began last year and the system enables follow-up analysis in Japan.

Primary Small Cell Carcinoma Of Lung With Metachronous Breast Metastasis

Abstract Breast metastases from an extra-mammary malignancy are rare. Among the lung malignancies that metastasise in the breasts, previous literature has described approximately 30 cases of NSCLC and only a few cases of SCLC. Here, we present a 54-year-old woman with metachronous breast metastasis from pulmonary small cell carcinoma. She presented with a soft tissue mass in the right lung hilum. After bronchoscopy with biopsy, SCLC was verified. Th e patient was given 4 cycles of etoposide and cisplatin followed by radiation therapy. Seven months after the diagnosis of primary lung cancer, the patient palpated a mass in her right breast. Clinical examination and further diagnostics revealed the suspected malignancy, and a radical mastectomy was performed. Immunohistochemical findings suggested metastatic SCLC in the breast. Differentiation between primary and metastatic cancer in the breast is very important for therapeutic planning

224P - Synchronous and metachronous breast cancer in Ukraine

224P - Synchronous and metachronous breast cancer in Ukraine

Abstract P2-07-05: Risk of metachronous contralateral breast cancer: Systematic review and meta-analysis

Abstract Introduction Over the last 2 decades, an increasing number of primary breast cancer (PBC) patients opted for a risk reducing contralateral mastectomy, to minimize risk of subsequent contralateral breast cancer (CBC). Therefore, accurate risk estimates of CBC are important for patient tailored counseling and decision making regarding treatment. Currently, CBC risk estimates are determined by BRCA1/2 mutation status, age at PBC diagnosis and family history. For other risk factors, results are inconclusive. We therefore aimed to quantify the association with CBC risk for patient, tumor and treatment related factors as reported in the literature. Methods Medline was searched for publications on CBC risk by one reviewer (DA). We focused on associations between CBC risk and BRCA1/2 and CHEK2*1100delC mutations, SNPs, risk-reducing salpingo-oophorectomy and various factors at PBC diagnosis: family history of breast cancer (BC), age, BMI, menopausal status, mammographic density, TNM-stage, receptor status, morphology, administered radiotherapy and adjuvant systemic treatment. Eligible papers were published in English between 01-01-1990 and 01-04-2015, investigated female patients with invasive early BC and reported relative risk (RR) estimates (i.e., hazard ratios, relative risks or odds ratios). We combined RR estimates using a random effects model. Heterogeneity was assessed using the I2 statistic. Forest plots for crude and adjusted estimates were generated stratifying for mutation status (i.e., BRCA1, BRCA2, CHEK2*1100delC), non-carriers and unselected patients (i.e., population/hospital based cohorts). Results After screening of 1,423 papers for title and abstract, 173 eligible papers were fully read, and 96 papers fulfilled the inclusion criteria. Both in the unselected group and in the BRCA1 and BRCA2 groups, administration of adjuvant endocrine therapy (vs. not), was associated with decreased CBC risk (RR, 0.62 (95% CI 0.55-0.69), 0.55 (95% CI 0.39-0.77), and 0.62 (95% CI 0.40-0.95), respectively). Adjuvant chemotherapy was associated with reduced CBC risk in unselected patients (RR 0.73; 95% CI 0.62-0.86). CBC risk was increased in unselected patients who received radiotherapy at age<40 years (vs. not) (RR 1.33; 95% CI 1.18-1.49), had a lobular (vs. ductal) PBC (RR 1.70; 95% CI 1.33-2.16), had a T2/T3 (vs. T1) PBC (RR 1.15; 95%CI 1.01-1.30), with BMI >30 (vs. <25) at PBC (RR 1.50; 95% CI 1.27-1.76) or had a positive family history for BC (vs. not) (RR 1.82; 95% CI 1.35-2.46). For the other factors of interest we did not observe any effects on CBC risk. For CHEK2*1100delC mutation carriers and non-carriers, information on factors affecting CBC risk was scarce. In non-carriers, the RR for adjuvant chemotherapy was 0.60 (95% CI 0.53-0.68). Conclusions In unselected patients, adjuvant systemic treatment for PBC decreases CBC risk while a lobular morphology of PBC, high BMI, and a family history of BC increase the risk of CBC. Data is scarce for carriers of a BRCA1/2 or CHEK2*1100delC mutation and non-carriers. This review identifies prognostic factors to consider for individualized CBC risk estimation which may support medical decision making in BC patients. Citation Format: Akdeniz D, Schmidt MK, McCool D, van den Broek AJ, Hauptmann M, Seynaeve CM, Steyerberg EW, Hooning MJ. Risk of metachronous contralateral breast cancer: Systematic review and meta-analysis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-05.

Abstract P2-02-07: Predicting germline mutations in BRCA1/2 and beyond: A comparison of women with single and multiple breast primaries

Abstract Synchronous or metachronous breast primaries are a well-known indication of hereditary breast cancer, particularly within BRCA1/2 mutation carriers. However, the frequency of gene mutations within this patient group has not been well defined, especially in the setting of multi-gene panel testing (MGPT). We conducted a retrospective review of mutation carrier status in a population of females with breast cancer(s), but no other reported cancer diagnoses, and who had MGPT at a single diagnostic laboratory. Among 31,864 females tested, the following were excluded from analysis: 5389 (17%) had variants of unknown significance (VUS), 133 (0.4%) had moderate risk mutations and 316 (1.0%) had MUTYH monoallelic mutations. For the remaining 26,026 females, we evaluated whether mutation status is associated with risk of multiple breast primaries using Fisher's exact test and logistic regression analysis adjusting for age at testing, age at first breast cancer diagnosis, and mutations in other genes. The number of genes analyzed ranged from 5-49, depending on the panel ordered. Gene-specific analyses were limited to with 10 or more mutations in this cohort (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CDKN2A, CHEK2, MRE11A, MUTYH, MSH6, NBN, NF1, PALB2, PMS2, PTEN, RAD50, RAD51C, RAD51D, and TP53). In this cohort the average age of first breast cancer diagnosis was 47.7 (range 12-95) and the average age of second diagnosis was 56 years (range 17-89). A positive result (pathogenic mutation or variant, likely pathogenic) in any gene was more likely for women with three or more breast cancer primaries (p=0.007) and two or more primaries (p=1.2e-08) than those with one breast primary. Overall, women with a mutation in any gene were more likely to have multiple primary breast cancers than those without mutations. Specifically, women with mutations in ATM, BRCA1, CDH1, PALB2, PTEN, and TP53 mutations were more likely to have multiple breast primaries than non-carriers of mutations in those genes (table 1). Table 1: Risk of multiple breast primaries in mutation carriers versus non-carriers No. (%) with multiple primaries GeneCarrierNon-CarrierOR (95% CI)p-valueATM55/262 (21%)2189/15057 (15%)1.6 (1.1, 2.2)0.006BRCA1100/526 (19%)3104/24117 (13%)1.9 (1.5, 2.4)3.2e-07CDH16/24 (25%)3338/25016 (13%)2.8 (1.0, 1.7)0.04PALB245/218 (21%)2199/15101 (15%)1.7 (1.2, 2.4).004PTEN7/28 (25%)3429/25788 (13%)3.8 (1.5, 8.9)0.003TP5319/96 (20%)3419/25787 (13%)2.4 (1.3, 4.0)0.002 Our results show that women with multiple breast primaries are more likely to have mutations in some genes than others. Interestingly, all genes with significant odds ratios are well-described and most are known to cause high risk for breast cancer, with the exception of ATM. Additional studies are needed to confirm these results and quantify risks for second primary breast cancers. With further work defining the risks of multiple primary breast cancers, this information could be implemented into clinical practice to aid women in risk management following a positive result. Citation Format: Panos Smith L, Tian Y, Qian D, McFarland R, Espenschied CR. Predicting germline mutations in BRCA1/2 and beyond: A comparison of women with single and multiple breast primaries [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-02-07.

TREATMENT OF TRIPLE-NEGATIVE BREAST CANCER

The rate of triple-negative breast cancer is 10–24 %, and in recent years it’s one of the most studied subtypes of breast cancer due to its clinical aggressiveness and a small number of molecular targets. The study objective is to evaluate effectiveness of different NAPCT regimens including their dependence on the presence of mutations in the ВRСА 1, 2, СHEK2 genes. Materials and methods . The study included 40 female patients with triple-negative breast cancer. The patients were monitored from 2012 to 2016; surgical treatment was performed at the P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia. Median patient age was 45.9 (31–69) years. All patients received neoadjuvant polychemotherapy (NAPCT) per different regimens. Then the patients underwent surgery of different volume (from radical mastectomies to resections), and in 25 % of cases reconstructive breast surgery was performed. In 5 patients with BRCA1, – 2 mutations, prophylactic subcutaneous mastectomy with immediate reconstruction with an implant was performed; 2 patients refused prophylactic mastectomy; in 1 patient with СНЕК2 mutation, metachronous multiple primary breast cancer was diagnosed, previously she didn»t undergo prophylactic mastectomy, and 6 years later cancer in the second breast was diagnosed. Results. The study included 11 patients under 40 (27.5 %), 4 (50 %) of them in the group with mutations in ВRCA1, -2, CHEK2. The study demonstrated high effectiveness of NAPCT regimens per the АС + Т scheme and weekly injections of doxorubicin 25 mg/m 2 , cisplatin 30 mg/m 2 , and paclitaxel 100 mg/m 2 . Grade IV treatment pathomorphosis for NAPCT per АС + Т scheme was achieved in 50.0 ± 7.9 % cases, for intensified regimen – in 62.5 ± 12.5 % cases. Median follow-up duration for this patient group was 22.1 months, and during this time disease progression was observed in 3 patients: in the 1st patient continued growth on the thoracic wall and brain metastases were diagnosed, in the 2nd patient – lung and supraclavicular lymph nodes metastases, in the 3rd patient – metastases in the cerebellum. In all of these patients, grade IV treatment pathomorphosis wasn»t achieved. Conclusions. The study demonstrated high effectiveness of NAPCT in patients with triple-negative breast cancer of different stages: objective response rate was 90.0 ± 4.7 %, grade IV treatment pathomorphosis was 50.0 ± 7.9 %. Grade IV treatment pathomorphosis for NAPCT per АС + Т scheme was achieved in 50.0 ± 7.9 % cases, for intensified regimen – in 62.5 ± 12.5 % cases. Rate of grade IV treatment pathomorphosis was higher in patients with hereditary form of the disease (62.5 ± 18.3 %) compared to the group with sporadic breast cancer (46.9 ± 8.8 %), р >0.05. In all patients, 2-year disease-free survival was 92.5 %, 2-year overall survival was 95 %.