Frequency of Occult Breast Cancer After Prophylactic Mastectomy Among High-Penetrance Breast Cancer Gene Positives
Condition: Genetic Predisposition; BRCA Mutation; Breast Cancer; Occult Cancer
MeSH terms: Breast Neoplasms; Genetic Predisposition to Disease
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Histopathological confirmation
Intervention type(s): Procedure
Intervention description(s): After mastectomy, each specimen will be assessed histopathologically for the presence or absence of invasive focus of breast cancer.
Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        All individuals who came out as genetic test positive for high-risk breast cancer genes;
        carriers/breast cancer patients and who opted for prophylactic risk-reducing mastectomy.