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Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants.

ABSTRACT: Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR-]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I-III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60-0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94-2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients' counseling on treatment, prevention, and surveillance strategies.

SUBMITTER: Lambertini M

PROVIDER: S-EPMC7880991 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants.

Lambertini Matteo M Ceppi Marcello M Hamy Anne-Sophie AS Caron Olivier O Poorvu Philip D PD Carrasco Estela E Grinshpun Albert A Punie Kevin K Rousset-Jablonski Christine C Ferrari Alberta A Paluch-Shimon Shani S Toss Angela A Senechal Claire C Puglisi Fabio F Pogoda Katarzyna K Pérez-Fidalgo Jose Alejandro JA De Marchis Laura L Ponzone Riccardo R Livraghi Luca L Estevez-Diz Maria Del Pilar MDP Villarreal-Garza Cynthia C Dieci Maria Vittoria MV Clatot Florian F Duhoux Francois P FP Graffeo Rossella R Teixeira Luis L Córdoba Octavi O Sonnenblick Amir A Ferreira Arlindo R AR Partridge Ann H AH Di Meglio Antonio A Saule Claire C Peccatori Fedro A FA Bruzzone Marco M t'Kint de Roodenbeke Marie Daphne MD Ameye Lieveke L Balmaña Judith J Del Mastro Lucia L Azim Hatem A HA

NPJ breast cancer 20210212 1

Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR-]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I-III inv ...[more]

PMID: 33579978

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Project description:ImportanceAlthough most women with BRCA-associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conservation is important.ObjectiveTo describe the clinical outcomes of women with BRCA-associated breast cancer who were treated with breast-conserving therapy, including the risks of ipsilateral and contralateral cancer events and bilateral mastectomy-free survival.Design, setting, and participantsThis cohort study conducted at a single-institution academic national comprehensive cancer center included 172 women identified from a prospectively maintained database who had pathogenic BRCA1/2 variants and were treated with breast-conserving therapy from January 1, 1977, to December 31, 2021.Main outcomes and measuresClinical and pathologic characteristics for patients with BRCA1 and BRCA2 were compared, and estimates of overall survival, bilateral mastectomy-free survival, distant disease-free survival, risk of ipsilateral breast cancer, and risk of contralateral cancer were computed.ResultsThe cohort included 172 women (mean [SD] age, 47.1 [11.7] years), with 42 (24.4%) receiving a diagnosis of breast cancer prior to 40 years of age. Compared with BRCA2 variant carriers (80 [46.5%]), women with BRCA1 variants (92 [53.5%]) were younger at breast cancer diagnosis and tended to have more advanced tumors, which were more likely to be hormone receptor negative and higher grade. At a median follow-up of 11.8 years (IQR, 5.7-18.2 years), estimates of 10-year survival and risk were: overall survival, 88.5% (95% CI, 83.1%-94.2%); bilateral mastectomy-free survival, 70.7% (95% CI, 63.3%-78.9%); risk of an ipsilateral breast cancer event, 12.2% (95% CI, 5.8%-18.2%); and risk of contralateral cancer, 21.3% (95% CI, 13.3%-28.6%). Risks continued to increase after 10 years of follow-up.Conclusions and relevanceIn this cohort study, although women with breast cancer and pathogenic BRCA1/2 variants treated with breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events, most did not have another cancer event and remained bilateral mastectomy free. These findings may be useful for informing patients with BRCA variants choosing breast conservation.

Project description:ImportanceMetaplastic breast cancer (MpBC) is a rare, heterogeneous disease often associated with inferior outcomes. A growing body of literature describes the clinical and molecular features of MpBC, yet limited data describe the pathogenic germline variants (PGVs) in breast cancer susceptibility genes among affected individuals.ObjectiveTo examine the frequency and types of PGVs in breast cancer genes among patients with MpBC.Design, setting, and participantsThis is a descriptive retrospective cohort study of patients who received a diagnosis of MpBC at the University of Pennsylvania between January 2010 and May 2023. Electronic medical records were reviewed for demographic, clinicopathologic, and germline genetic testing information. Germline variant status was independently confirmed by a licensed genetic counselor and a physician with expertise in genetics. MpBC diagnosis and subtype were confirmed by a breast pathologist. Participants were identified via query of an institutional pathology database for reports signed between January 2010 and May 2023 including the term metaplastic. Among 320 initially obtained reports, 272 individuals had confirmed MpBC and were included in the study.ExposureGermline genetic testing to investigate the presence of PGVs in breast cancer susceptibility genes.Main outcomes and measuresThe primary outcome measurement was the prevalence of PGVs in breast cancer susceptibility genes among participants. The hypothesis that individuals with MpBC have an enrichment of PGVs in genes associated with inherited breast cancer risk was formulated before data collection.ResultsThe total sample size was 272 women, and the median age at diagnosis was 58 years (range, 20-102 years); all were biological female patients; 143 of 272 (52.6%) had documentation of germline genetic testing; and participants with testing were significantly younger than those without (median age, 53 years [range, 20-79 years] vs 63 years [range, 29-102 years]; P < .001). Of the 143 patients, 24 (16.8%) had a PGV in a breast cancer susceptibility gene (BRCA1, n = 17; BRCA2, n = 5; PALB2, n = 1; CHEK2, n = 1). Patients with PGV-associated MpBC received a diagnosis at a younger age than those with sporadic disease, but there were no significant differences in hormone receptor positivity, ERBB2 status, or metaplastic subtype.Conclusions and relevanceIn this cohort study of patients with MpBC, a substantial proportion of clinically tested patients had a PGV in a breast cancer susceptibility gene, most commonly BRCA1. Germline testing was high yield in patients with MpBC, many of whom would be included in current germline testing eligibility criteria.

Project description:BackgroundKnowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants.Patients and methodsThis is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy.ResultsAmong the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group.ConclusionThis study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.

Dataset Information

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants.

Publications

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants.

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