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Lower mitotic activity in BRCA1/2-associated primary breast cancers occurring after risk-reducing
Victorien Mt van Verschuer1, Bernadette Am Heemskerk-Gerritsen2, Carolien Hm van Deurzen3
1Department of Surgical Oncology; Erasmus MC Cancer Institute; Rotterdam, the Netherlands.
Abstract:
Risk-reducing salpingo-oophorectomy (RRSO) is associated with 50% reduction of BRCA1/2-associated breast cancer (BC) risk, possibly through decreased growth activity. In this pilot study, tumor characteristics and growth rates of BRCA1/2-associated primary BCs (PBCs) detected after RRSO were compared with those of PBCs originating without RRSO. From a cohort of 271 women with BRCA1/2-associated screen detected BC, we selected 20 patients with PBC detected ≥12 months after RRSO (RRSO group). Controls were 36 BRCA1/2 mutation carriers with PBC detected without RRSO (non-RRSO group) matched for age at diagnosis (± 2.5 y) and for BRCA1 or BRCA2 mutation. Pathology samples were revised for histological subtype, tumor differentiation grade, mitotic activity index (MAI), estrogen receptor (ER), progesterone receptor (PR), and HER2 status. Tumor growth rates, expressed as tumor volume doubling times (DT), were calculated from revised magnetic resonance and mammographic images. Median age at PBC diagnosis was 52 y (range 35-67). PBCs after RRSO had lower MAIs (12 vs. 22 mitotic counts/2 mm, P = 0.02), were smaller (11 vs. 17 mm, P = 0.01), and tend to be PR-positive more often than PBCs without RRSO (38% vs. 13%, P = 0.07). Differentiation grade, ER, and HER2 status were not different. Median DT was 124 d (range 89-193) in the RRSO group and 93 days (range 54-253) in the non-RRSO group (P = 0.47). BC occurring after RRSO in BRCA mutation carriers features a lower MAI, suggesting a less aggressive biological phenotype. When confirmed in larger series, this may have consequences for BC screening protocols after RRSO.
Insights
Risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers may lead to less aggressive breast cancer (BC). Tumors detected after RRSO showed lower mitotic activity index, suggesting a potentially slower growth rate.
Area of Science:
- Oncology
- Genetics
- Radiology
Background:
- Risk-reducing salpingo-oophorectomy (RRSO) significantly reduces breast cancer (BC) risk in BRCA1/2 mutation carriers.
- The impact of RRSO on the biological characteristics and growth kinetics of subsequent primary breast cancers (PBCs) in this population is not well understood.
Purpose of the Study:
- To compare tumor characteristics and growth rates of BRCA1/2-associated PBCs detected after RRSO with those detected in BRCA1/2 mutation carriers without RRSO.
Main Methods:
- A pilot study compared 20 women who developed PBC after RRSO (RRSO group) with 36 matched BRCA1/2 mutation carriers without RRSO (non-RRSO group).
- Tumor characteristics (histological subtype, grade, mitotic activity index [MAI], ER, PR, HER2 status) were assessed.
- Tumor growth rates were calculated using tumor volume doubling times (DT) from MRI and mammographic images.
Main Results:
- PBCs in the RRSO group exhibited significantly lower MAIs (12 vs. 22, P=0.02) and were smaller (11 vs. 17 mm, P=0.01) compared to the non-RRSO group.
- A trend towards higher progesterone receptor (PR)-positivity was observed in the RRSO group (38% vs. 13%, P=0.07).
- No significant differences were found in differentiation grade, estrogen receptor (ER), or HER2 status. Median tumor doubling times were not significantly different (124 days vs. 93 days, P=0.47).
Conclusions:
- Breast cancer occurring after RRSO in BRCA mutation carriers may present with a less aggressive biological phenotype, characterized by lower MAI.
- These findings, if confirmed in larger studies, could inform future BC screening protocols for women who have undergone RRSO.
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