BRCA1 and BRCA2 gene mutations significantly increase the risks of breast and ovarian cancers. Screening for these mutations allows for increased surveillance and risk-reducing procedures that can improve health outcomes. Specifically: - BRCA1/2 mutation carriers have a 40-80% risk of developing breast cancer and a 11-40% risk of ovarian cancer. - Bilateral risk-reducing mastectomy can decrease breast cancer risk by at least 90% for carriers. Bilateral risk-reducing salpingo-oophorectomy can reduce ovarian and breast cancer risks by approximately 80% and 50% respectively. - Genetic testing costs around 23k in India and allows high-risk families and individuals to

1. DR SHARDA JAIN DR. JYOTI AGARWAL
Director : Lifecare Centre Director : Lifecare Centre
Lifecare IVF Lifecare IVF
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Why Screening BRCA 1 & II
Breast Cancer is the number one cancer among Indian women*
Estimate that by 2020, India could have as many as 1.8 Million cases of Breast Cancer
Cancer Type General Population
Risk
Mutation Risk
BRCA1 BRCA2
Breast 12% (in India 5-8%) 50%-80% 40%-70%
Second primary
breast
3.5% within 5 years
Up to 11%
27% within 5 years
12% within 5 years
40%-50% at 20
years
Ovarian 1%-2% 24%-40% 11%-18%
Clinicians, gynaecologists should :
Record detailed family and personal history in every case of breast, ovarian, colon & endometrial cancer and
offer genetic testing in appropriate families
Genetic testing offers the possibility of risk evaluation . if positive risk increase many fold . timely management
is applicable even in the pre-symptomatic stage
Many patients are quite aware of the possibility of familial cancers and request testing – but misinformation is
widespread
BRCA 1 & 2 mutations can be diagnosed easily and have defined inheritance patterns.
Both Somatic & Germline mutations are useful in guiding management of patients.
Autosomal Dominant Inheritance
BRCA – IMPORTANCE IN HEREDITARY
BREAST & OVARIAN CANCER

2. Potential Benefits:
 Clinical intervention may improve outcome
 Family members at risk can be identified
 Positive health behavior can be reinforced
 Reduction of uncertainty of screening BRCA I & II
You must know that Statistically significant decreased age of onset is seen in next generation
– 7.9 years from mother to daughter for BRCA1 & BRCA2 mutations
[Litton JK et al. Cancer 2012: 118: 321-5]
– 6.8 years for BRCA1 & 12.1 years for BRCA2-mutation positive individuals & earlier age of onset
was associated with progressive telomere shortening
[Martinez-Delgado et al. PLoS Genetics 2011: 7: e10021182]
Risk Reduction Mastectomy (RRM)
Bilateral risk reduction mastectomy (RRM) decreased the risk of developing breast cancer by at least 90% in
moderate- to high-risk women and in known BRCA1/2 mutation carriers.
[Hartmann LC et al. J Natl Cancer Inst 2001; 93: 1633-1637]
Option of RRM to be offered on a case-by-case basis after appropriate counseling including risks & benefits of
surgery & surgical breast reconstruction options
BRCA TESTING IN OVARIAN CANCER
BRCA 1 gene is located in chromosome 17q21 & its mutation causes ovarian cancer in 40 – 45% cases.
BRCA 2 gene is located in chromosome 13 Q13 & its mutation causes ovarian cancer in only 12-20% cases . the
mutation of both genes increases life time risk of women to develop ovarian cancer by 65-75%.
 NCCN advocates BRCA testing in all women with serous epithelial ovarian cancers – 20-25% women
positive even without family history
 Respond better to chemotherapy.
 FDA (May 2015) has approved OLAPARIB for use in BRCA positive ovarian cancers who relapse
What need to be done ?
Bilateral Risk Reducing Salpingo-oophorectomy (RRSO)
Absence of early methods of early detection & poor prognosis associated with advanced ovarian cancer
warrant RRSO in women after completion of child bearing or earlier than 40 years .
A meta-analysis of 10 studies showed approximately 80% reduction in the risk of ovarian or fallopian cancer
following RRSO
[Rebbeck TR et al. J Natl Cancer Inst 2009; 101:80-87]
RRSO also reduces the risk of breast cancer in carriers or BRCA mutations by ~50%
[Eisen A et al. J Clin Oncol 2005; 23: 7491-7496]
Gynaecologists should know that BRCA 1 & BRCA testing is possible in India it costs 23k
for combo screening (Cytogene)
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Contact : Shalabh.Saxena
M : 95484-66660