Patients with young-onset breast cancer who carry a BRCA mutation have similar survival as non-carriers. However, BRCA mutation carriers with triple-negative breast cancer might have a survival advantage during the first few years after diagnosis compared with non-carriers. Decisions about timing of additional surgery aimed at reducing future second primary-cancer risks should take into account patient prognosis associated with the first malignancy and patient preferences.
For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio [HR] for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for ≥2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend)
Background: The 70-gene signature MammaPrint has been shown to identify breast cancer patients for whom adjuvant chemotherapy (CT) could be safely omitted even in the presence of unfavorable standard clinical-pathological criteria. The MINDACT primary endpoint at 5 years median follow-up was met in 2016 (Cardoso et al, NEJM 2016) with a distant metastasis free survival (DMFS) rate at 5 years of 94.7% (95% CI: 92.5-96.2) in clinical high (C-High) / genomic low (G-Low) risk patients who received no CT. Longer follow-up is now available.
Methods: 6693 patients were enrolled in the prospective phase III randomized MINDACT study (EORTC 10041/BIG3-04) between 2007-2011. We assessed the DMFS rate at 5 years in the primary test (PT) population of C-High / G-Low patients who were randomized to receive no CT (n = 644). As secondary analysis, we evaluated DMFS and overall survival (OS) in the intention to treat (ITT) population of the C-High / G-Low group randomized to CT vs no CT (n = 749 and 748 respectively). Comparisons between CT and no CT groups are low-powered. We used Kaplan-Meier estimates for time to event endpoints and hazard ratios (HR) with 95% CI from cox-regression models adjusted for stratification factors used for the randomization.
Results: The median follow-up is 8.7 years, resulting in an updated 5-year DMFS rate for the PT population of C-High / G-Low patients with no CT of 95.1% (95% CI 93.1-96.6). The updated outcomes of the ITT population of C-High / G-Low patients are shown in the table. Further analyses will update the suggested age-dependent effect of CT omission for luminal breast cancer seen at 5 years in pre- versus post-menopausal women as in Tailor-X (Piccart et al, SABCS 2019).
Conclusions: The primary DMFS endpoint at 5 years continues to be met in CT untreated C-High / G-Low risk women, confirming MINDACT as a positive de-escalation study. With longer follow-up and in line with the natural history of luminal breast cancer, more distant relapses do occur but the estimated gain of 2.6% for CT administration in C-High / G-Low patients remains small in light of CT harmful effects. The level IA evidence for the clinical utility of the 70-gene signature for adjuvant CT decision making is maintained
Background: The impact of tumor focality on type of surgery, local recurrence rate, and survival after neoadjuvant chemotherapy (NACT) for breast cancer is not fully understood. This study aimed to compare local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) according to focality stratified by type of surgery and pathologic complete response (pCR), with a focus on breast conservation.
Methods: Participants (n = 6,134) in the GeparTrio, GeparQuattro, and GeparQuinto trials with operable or locally advanced tumors receiving NACT were classified as having unifocal (1 lesion), multifocal (≥ 2 lesions in 1 quadrant), or multicentric (≥ 1 lesion in ≥ 2 quadrants) disease. The study investigated LRFS, DFS, and OS according to focality stratified by type of surgery and pathologic complete response.
Results: The patients were classified as having unifocal (n = 4,733, 77.1 %), multifocal (n = 820, 13.4 %), or multicentric (n = 581, 9.5 %) tumors. The respective pCR rates were 19.4, 16.5, and 14.4 %. Breast conservation was performed for 71.6, 58.5, and 30 % of these patients, respectively (P < 0.001). The LRFS rate was 92.9 % for the unifocal, 95.1 % for the multifocal, and 90.4 % for the multicentric tumors (P = 0.002). The patients with multicentric tumors but not the patients with multifocal tumors had worse DFS (P < 0.001) and OS (P = 0.009) than the patients with unifocal tumors. However, LRFS, DFS, and OS were not inferior for the patients with multicentric or multifocal tumors if pCR was achieved or breast conservation was performed after NACT.
Conclusion: Breast conservation is feasible for clinically multifocal or multicentric breast cancer patients who undergo NACT without worsening LRFS if tumor-free margins can be attained or if patients achieve a pCR
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