High risk of in-breast tumor recurrence after BRCA1/2-associated breast cancer

Abstract

The purpose of the study was to compare breast-conserving therapy (BCT) and mastectomy (M) in BRCA1/2 mutation carriers. Women with invasive breast cancer and a pathogenic mutation in BRCA1 or BRCA2 were included in the study (n = 162). Patients treated with BCT (n = 45) were compared with patients treated with M (n = 118). Endpoints were local recurrence as first recurrence (LR), overall survival (OS), breast cancer death, and distant recurrence. Cumulative incidence was calculated in the presence of competing risks. For calculation of hazard ratios and for multivariable analysis, cause-specific Cox proportional hazards regression was used. Compared to M, BCT was associated with an increased risk of LR in univariable analysis (HR 4.0; 95 % CI 1.6–9.8) and in multivariable analysis adjusting for tumor stage, age, and use of adjuvant chemotherapy (HR 2.9; CI 1.1–7.8). Following M, all local recurrences were seen in the first 5 years after breast cancer diagnosis. Following BCT, the rate of LR continued to be high also after the first 5 years. The cumulative incidence of LR in the BCT group was 15, 25, and 32 % after 5, 10, and 15 years, respectively. There were no significant differences between BCT and M for OS, breast cancer death, or distant recurrence. BRCA1/2 mutation carriers treated with BCT have a high risk of LR, many of which are new primary breast cancers. This must be thoroughly discussed with the patient and is an example of how rapid treatment-focused genetic testing could influence choice of treatment.

Unusual recurrence of breast cancer in a BRCA‐variant patient after fat grafting

“…This is somewhat uncommon timing compared to the literature. As previously discussed, the overall risk of locoregional recurrence for patients undergoing mastectomy is 5%‐10% over 10 years; however, for BRCA‐positive patients, this risk increases to 15% and 25% after 5 and 10 years, respectively . For the patient discussed in this report, the BRCA‐associated risk of locoregional recurrence is more difficult to assess.…”

“…As previously discussed, the overall risk of locoregional recurrence for patients undergoing mastectomy is 5%-10% over 10 years; however, for BRCA-positive patients, this risk increases to 15% and 25% after 5 and 10 years, respectively. 13 For the patient discussed in this report, the BRCA-associated risk of locoregional recurrence is more difficult to assess. As previously noted, the patient underwent genetic testing and was determined to have a T37K variant, a missense mutation in the BRCA1 ring finger domain.…”

Clinical relevance of normal and tumour cell radiosensitivity in BRCA1/BRCA2 mutation carriers: A review

“…1.1e7.8) [59]. While all inbreast events were observed in the first 5 years in the Table 3 Rates of cause-specific and overall survival following breast conserving surgery and PORT in BRCA1 e BRCA2 carriers compared with controls.…”

“…Therefore, caution is urged when analyzing the results of retrospective studies on local control in early stage BRCA1/2 mutation-associated breast cancer patients. Table 1 shows that the majority of the reports did not find any significant difference in in-breast events between carriers and noncarriers [28,37,43,50,51,58,59]. In one of the few studies linking a significantly higher risk of local failure over time to the presence of a BRCA1/2 mutation, Haffty et al, using a multivariate step-wise Cox regression analysis adjusted for age, identified BRCA1/2 mutation status to be an independent predictor for IBTR with 49% tumour events observed in patients with a BRCA1/2 mutation vs 21% in the control group after 12-year follow-up (p ¼ 0.007) [40].…”

Was Angelina Jolie Right? Optimizing Cancer Prevention Strategies Among BRCA Mutation Carriers

“…We have excluded this therapy option, as a strong riskreducing effect of chemoprevention for all age groups and mutation types is uncertain (Duffy andNixon 2002, King et al 2001). The risk of breast cancer recurrence or a contralateral breast cancer (i.e., a new tumor in the opposite breast of the original tumor) is significant for mutation carriers (Graeser et al 2009, Nilsson et al 2014. As the state space structure does not account for recurrences or contralateral breast cancer and these states would alter a carrier's mortality, our model is limited by the accuracy of the breast cancer mortality rate.…”