Frequency of Occult Breast Cancer After Prophylactic Mastectomy Among High-Penetrance Breast Cancer Gene Positives

Recent studies have shown the rising incidence of Hereditary Breast Cancer (HBC) among Pakistani females, with growing numbers of Prophylactic Risk Reducing Mastectomies (PRRM) being offered to diagnosed cases of HBCs across different centres in the country.1 HBCs are seen in 5 to 10% of cases with Breast Cancers(BC). The main identified genes which contribute to the development of BCs among HBC patients are BRCA1, BRCA2, CDH1, PALB2, PTEN, TP53, ATM, BARD1, CHEK2, NF1, RAD51C/D and STK11. Among these culprit genes, BRCA1 and BRCA2 contribute to most HBC cases.

The role of Sentinel Lymph Node Biopsy(SLNB) among mutation-negative BC patients is well established; however, we are lacking data to assess the role of sentinel lymph node biopsy for patients who are undergoing surgery for prophylactic reasons without proven malignancy. Literature has reported a positive Occult Breast Cancer (OBC) rate of 0 to 11.3% among mastectomy specimens which are removed prophylactically. Majority of the time when the invasive focus is diagnosed in prophylactic mastectomy specimens they are found to be in-situ cases where axillary Staging using SLNB can be exempted; however, when the OBC is identified even in prophylactic mastectomy specimens, axilla should be addressed accordingly. Albeit SLNB has associated complications with it; postoperative pain, lymphedema, paresthesia and rare reaction to the injected dye. Therefore the question here arises regarding skipping SLNB among patients who are undergoing PRRMs without proven malignancy pre-operatively. However, before standardizing the practice in our population we need convincing evidence that the frequency of OBC is low among our patients. By identifying the true prevalence of OBC among our gene-positive HBC patients who are opting for PRRM, we would be able to skip SLNB; as not only it has psychological implications but also adds a financial burden on patients and families due to the addition of an extra procedure and hospital bills; as the financial and socioeconomic status of our population has already declined over last few years due to the economic crises faced worldwide, specifically after-affects are seen in Lower Middle-Income Country(LMIC) like Pakistan.

Due to the inflated cost and added procedure of SLNB in PRRM cases, our primary aim of this study is to evaluate the frequency of OBC among patients who underwent PRRMs concerning their high penetrance BC gene positivity; with the goal that SLNB can be safely omitted for PRRMs or not. Our secondary goal is to correlate the radiological findings with final histopathological results among OBC-positive patients, also the histopathological pattern of HBC genes among our cohort.

Inclusion criteria

• individuals with positive genetic test results for High-Penetrance Hereditary BC genes, and those who had PRRMs at our center

Exclusion criteria

• individuals who did not give consent and those who had already diagnosed bilateral BCs