Breast cancer surveillance for BRCA1/2 mutation carriers – is “early detection” early enough?

Abstract

Background Annual MRI screening is associated with a significant reduction in advanced-stage breast cancer diagnosis in BRCA1/2 mutation carriers. The impact that early detection has on subsequent oncological treatment is less frequently reported. In this study we compared disease stage and therapeutic approaches in BRCA1/2 mutation carriers who developed breast cancer while adhering to the recommended surveillance scheme (“known carriers”), with women who became aware of their BRCA mutation status after breast cancer diagnosis (“latent carriers"). Methods Data on tumor characteristics, disease stage, and therapeutic decisions were collected on BRCA1/2 mutation carriers treated for breast cancer at the Chaim Sheba Medical Center. Results Data were available for 298 BRCA1/2 carriers. Median follow-up was 77.4 months (range, 3.5–520). Age at diagnosis was not statistically different between known carriers (n = 96; median age at diagnosis 44.7 years) and latent carriers (n = 202; 43.7 years); p = 0.8284. Of known carriers, 19.8% were diagnosed with carcinoma in situ vs. 5% of latent carriers (p = 0.0012). Stage T1N0 disease was diagnosed in 54/96 (56.3%) of known carriers vs. 59/202 (29.2%) of latent carriers (p < 0.00001). Neoadjuvant or adjuvant chemotherapy was administered to 46/96 (47.9%) of known carriers compared with 162/202 (80.2%) of latent carriers (p < 0.00001). Conclusions While early stage breast cancer was diagnosed frequently among known BRCA1/2 carriers under tight surveillance, almost half of these women were treated with chemotherapy. Healthy BRCA1/2 mutation carriers should be informed about these rates while discussing risk-reducing surgical options.

Management of patients with BRCA mutation from the point of view of a breast surgeon

“…It is debated whether the detection of a breast cancer in a woman choosing surveillance is early enough. Even under tight surveillance the breast cancer diagnosed in BRCA patients are more aggressive and therefore more often require adjuvant chemo- and/or endocrine therapy [ 98 ].…”

Controversies and Open Questions in Management of Cancer-Free Carriers of Germline Pathogenic Variants in BRCA1/BRCA2

“…Heemskerk-Gerritsen et al found that RRM was associated with lower overall (hazard ratio 0.4) and breast cancer-specific (hazard ratio 0.06) mortality for BRCA1 P/LPV carriers, but not BRCA2 P/LPV carriers in a multicenter cohort study [ 46 ]. As expected, lower cancer rates would result in lower rates of cancer treatment [ 47 , 48 ], which can be associated with significant morbidity and reduced quality of life. Skin-sparing mastectomy with or without nipple-areolar complex preservation followed by immediate breast reconstruction is becoming the preferred surgical approach given the superior cosmetic results [ 49 , 50 ].…”

“…The impact of MRI screening on survival is not clear, despite the stage shift at diagnosis. Although a small retrospective study from Israel suggested a possible survival advantage for BRCA P/LPV carriers who decline RRM and develop breast cancer during intensive follow-up compared with unscreened carriers (unaware of their genetic status) [ 47 ], a larger study from another tertiary center in Israel did not demonstrate the same positive outcomes [ 48 ]. Potential disadvantages for MRI use at annual intervals include higher costs compared with mammography (MG), higher false-positive rates [ 81 ], and limited availability in certain geographical regions within the country.…”

“…Since screening for cancer does not actively reduce cancer risk but only offers a passive way to a possible earlier stage at diagnosis (with an unclear effect (if any) on survival), in a sizeable number of cases having to endure morbid oncological treatments [ 48 ], the importance of new risk-reducing strategies is self-evident. The existing options of rrBSO in premenopausal women and RRM have significant psychological and quality-of-life impacts, some of which are not optimally addressed.…”

A Cost Decision Model Supporting Treatment Strategy Selection in BRCA1/2 Mutation Carriers in Breast Cancer

“…The cost analysis upon which the decision-making model was built has much greater importance in the investigated setting where efficacy data are controversial, such as long-term survival in the various clinical paths. In the context of BRCA-mutated subjects, the pathway with the addition of periodic MRI leads to a higher number of early T1N0 diagnoses (56.3% vs. 29.2%), in diagnosis-positive lymph nodes (11.5% vs. 48.5%), and to a lower number of chemotherapies administered (47.9% vs. 80.2%) [ 55 ]. However, despite these data, the real impact of MRI on mortality reduction is still uncertain, particularly in BRCA2 carriers [ 9 ].…”