372P - Prevalence of BRCA1 and BRCA2 mutation among Indian breast cancer patients: A multicentre cross-sectional study

Background

Germline mutations in breast cancer susceptibility genes 1 or 2 (gBRCA1/2mut) increase predisposition to breast cancer. Previous Indian breast cancer studies suggest gBRCAmut prevalence of 18.6-36.2%, but data are either single-centre or in patients selected by family history, histopathological subtype or age.

Methods

This was a prospective,cross-sectional,multicentre, study conducted in 14 institutions across India among patients with newly diagnosed stage I to IV breast cancer who had not yet completed 1st- line treatment and were not enriched for gBRCAmut. Based on previous Indian data, a sample size of 313 was estimated to be adequate. Germline BRCA 1/2 testing was performed in a single central laboratory in blood sample-derived DNA by next-generation sequencing (NGS), with reflex multiplex ligation probe amplification (MLPA) in patients who were -ve on NGS or were detected with Variant of Unknown Significance (VUS).

Results

Between June 2022 and Feb 2023, 304 patients were recruited in the study with a median age of 46 (22-83) years.The prevalence of pathogenic or likely pathogenic (P/LP) gBRCA 1/2 mutation was 27 (8.8%, 95%CI 6.18-12.61%) in the full study population. P/LP gBRCAmut prevalence in patients with ER/PR+/HER2 negative, HER2 positive and TNBC were 10/123 (8.13%, 95% CI 4.48-14.32), 2/80 (2.5%, 95% CI 0.69-8.66), and 15/102 (14.8%, 95% CI 9.12-22.85) respectively; in patients ≤ 50 years and >50 years were 20/194 (10.31%, 95% CI 6.77-15.39) and 7/110 (6.37%, 95% CI 3.12-12.56) respectively; in patients with and without relevant family history were 10/35 (28.57%, 95% CI 16.33-45.05) and 17/269 (6.32%, 95% CI 2.57-7.63 ), respectively; and in patients with stage I-III and stage IV disease were 22/235 (9.36%, 95% CI 6.26-13.77) and 5/68 (7.35%, 95% CI 3.18-16.09), respectively. The majority of P/LP gBRCAmut were in BRCA1 (16/304, 5.26%, 95%CI 3.04-8.4%), of whom 12/16 (75.0%) patients had TNBC, while 11/304 (3.62%) patients had gBRCA2mut of whom 7/11 (63.63%) had ER/PR+/HER2 -negative disease and 4/11 (36.37%) were TNBC.

Conclusions

Less than 10% of unselected newly diagnosed Indian breast cancer patients have P/LP gBRCA mutations. Younger age, TNBC subtype and positive family history enrich for such mutations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

AstraZeneca Pharma India Ltd.

Funding

AstraZeneca Pharma India Ltd.

Disclosure

S. Nag: Financial Interests, Personal, Invited Speaker: Dr Reddys Pfizer Roche; Financial Interests, Institutional, Local PI: AstraZeneca. Roche; Non-Financial Interests, Advisory Role: NGO s like WCI. IMA; Non-Financial Interests, Member: ASCO. ISMPO. R. Kodagali: Financial Interests, Personal, Full or part-time Employment: AstraZeneca Pharma India Ltd. K. Bhatt: Financial Interests, Personal, Full or part-time Employment: AstraZeneca Pharma India Ltd. S. Gupta: Financial Interests, Personal, Other, Member of various committees related to guidelines, drug pricing, others: Indian Council of Medical Research, Government of India; Financial Interests, Personal, Other, Member of Scientific Committee on nano-biosensors for healthcare applications: Council of Scientific and Industrial Research, Government of India; Financial Interests, Personal, Other, Scientific committee member for appraisal of scientific projects submitted to DBT for funding.: Department of Biotechnology, Government of India; Financial Interests, Personal, Other, Scientific committee member for appraisal of scientific projects submitted to India Alliance for funding. India Alliance is a partnership between Wellcome Trust and Department of Biotechnology (Government of India) to fund healthcare related research in India.: India Alliance; Financial Interests, Institutional, Other, Steering Committee member for a global clinical trial (CLEE011A2207). Honorarium to institution.: Novartis; Financial Interests, Institutional, Other, Steering Committee member for a global clinical trial. Honorarium to institution.: AstraZeneca; Financial Interests, Institutional, Advisory Board, Advisory Board member on ovarian cancer. Honorarium to institution.: AstraZeneca UK Limited; Financial Interests, Institutional, Advisory Board, Advisory Board member on metastatic breast cancer. Honorarium to institution.: Eli Lilly & Company (India) Limited; Financial Interests, Institutional, Invited Speaker, Invited speaker on cervical cancer at an academic conference. Honorarium to institution: Seoul National University Hospital; Financial Interests, Institutional, Invited Speaker, Chairperson at a conference. Honorarium to institution: Lupin Limited; Financial Interests, Institutional, Invited Speaker, Chairperson, speaker, or panelist at 5 conferences/meetings. Honoraria to institution.: Roche Products (India) Private Limited; Financial Interests, Institutional, Invited Speaker, Chairperson, panelist, or speaker at a 3 meetings/roundtable. Honoraria to institution: Novartis Healthcare Pvt. Ltd.; Financial Interests, Institutional, Invited Speaker, Chairperson at 2 conferences/meetings. Honoraria to institution: Eli Lilly & Company (India) Limited; Financial Interests, Institutional, Invited Speaker, Invited speaker in a conference. Nag Foundation is a not-for-profit registered society working in the field of cancer: Nag Foundation; Financial Interests, Institutional, Invited Speaker, Invited panelist in a meeting. Honorarium to institution.: Eisai Company Limited; Financial Interests, Institutional, Invited Speaker, Invited speaker. Honorarium to institution: Omnicuris Healthcare Private Limited; Financial Interests, Institutional, Invited Speaker, Invited panelist at a conference. Honorarium to institution.: Cipla Limited, Cadila Pharmaceuticals; Financial Interests, Institutional, Invited Speaker, Invited chairperson at a conference. Honorarium to institution.: Intas Pharmaceuticals Limited; Financial Interests, Institutional, Local PI, CO40016 Titled - A Double Blind, Placebo- Controlled, Randomized Phase III Study of IPATASERTIB in combination with Paclitaxel As a treatment for patients with PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple Negative Breast cancer or Hormone Receptor – Positive, HER2 – Negative Breast Cancer: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Coordinating PI, National coordinating PI of a multi-omics study in ER positive breast cancer: Department of Biotechnology, Government of India; Financial Interests, Institutional, Local PI, EGC002: Phase III, Randomized, Multicenter, Double-blind Study to Compare Efficacy and Safety of EG12014 (EirGenix Trastuzumab) with Herceptin® as Neoadjuvant Treatment in Combination with Anthracycline/Paclitaxel-based Systemic Therapy in Patients with HER2-positive Early Breast Cancer: EirGenix Inc.; Financial Interests, Institutional, Local PI, Protocol No. - CLEE011A3201C : A phase II randomized study of the combination of Ribociclib plus goserelin acetate with Hormonal Therapy versus physician choice chemotherapy in premenopausal or perimenopausal patients with hormone receptor positive/HER2-negative inoperable locally advanced or metastatic breast cancer - RIGHT Choice Study: Novartis Healthcare Pvt. Ltd.; Financial Interests, Institutional, Local PI, Protocol No. - D9100C00001 : A Phase III, Randomized, Multi-Center, Double-Blind, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With and following Chemoradiotherapy Compared to Chemoradiotherapy Alone for Treatment in Women With Locally Advanced Cervical Cancer (CALLA): AstraZeneca Pharma India limited.; Financial Interests, Institutional, Local PI, Protocol No. - CLEE011A2207 : A phase II, multicenter, randomized, open-label study to evaluate the safety and efficacy of 400 mg of ribociclib in combination with non-steroidal aromatase inhibitors for the treatment of pre- and postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer who received no prior therapy for advanced disease: Novartis Healthcare Pvt. Ltd.; Financial Interests, Institutional, Local PI: Glenmark Pharmaceuticals Ltd.; Financial Interests, Institutional, Coordinating PI, Protocol No. - D0816R00025 : A Prospective, Multicentre, Phase-IV Clinical Trial of Olaparib in Indian Patients with Platinum Sensitive Relapsed Ovarian Cancer who are in Complete or Partial Response Following Platinum Based Chemotherapy and Metastatic Breast Cancer with Germline BRCA1/2 Mutation (SOLI Study): AstraZeneca Pharma India Limited; Financial Interests, Institutional, Local PI, Protocol No. - D9670C00001 : A Phase 3, Randomized, Multi-center, Open-label Study of Trastuzumab Deruxtecan (T-DXd) Versus Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive Breast Cancer Patients whose Disease has Progressed on Endocrine Therapy in the Metastatic Setting (DESTINY-Breast06): AstraZeneca Pharma India Ltd.; Financial Interests, Institutional, Local PI, Protocol No. - D3614C00001 : A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib + Paclitaxel Versus Placebo + Paclitaxel as First-line Treatment for Patients with Histologically Confirmed, Locally Advanced (Inoperable) or Metastatic Triple-Negative Breast Cancer (TNBC).: AstraZeneca Pharma India Limited; Financial Interests, Institutional, Local PI, PIK3CA Registry- A descriptive study of PIK3CA mutations in patients with HR+/Her2- advanced breast cancer.: NOVARTIS HEALTHCARE PRIVATE LIMITED; Financial Interests, Institutional, Local PI, Protocol No. - D967JC00001 : A Phase 1b/2 Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination with other Anti-cancer Agents in Patients with HER2-positive Metastatic Breast Cancer (DESTINY-Breast07): AstraZeneca Pharma India Ltd.; Financial Interests, Institutional, Local PI, D9311C00001 ''A Randomised, Multicentre, Double-blind, Placebo-controlled, Phase III Study of First-line Carboplatin and Paclitaxel in Combination with Durvalumab, Followed by Maintenance Durvalumab with or without Olaparib in Patients with Newly Diagnosed Advanced or Recurrent Endometrial Cancer (DUO-E): AstraZeneca; Financial Interests, Institutional, Local PI, WO42633 A phase III, randomized, double-blind,placebo-controlled clinical trial to evaluate the efficacy and safety of adjuvant atezolizumab or placebo and trastuzumab emtansine forher2-positive breast cancer at high risk of recurrence following preoperative therapy (ASTEFANIA study): Roche Products (India) Pvt. Ltd.; Financial Interests, Institutional, Local PI, MO42921 A multi-country observational retrospective study to evaluate the prevalence of pd-l1 and its role in patients with tnbc treated with systemic therapy (VANESSA): Roche Products India Pvt Ltd.; Financial Interests, Institutional, Local PI, Cost-effectiveness Analysis & Value-Based Pricing for Anti-Cancer Drugs: Implications for Patients, Industry, Insurer and Regulator: Department of Health Research, Ministry of Health and Family Welfare, New Delhi; Financial Interests, Institutional, Coordinating PI, Coordinating PI for Multi-Omics Analysis to Decipher Mechanisms of Hormone Resistance in Breast Cancer: Department of Biotechnology, Government of India; Financial Interests, Institutional, Coordinating PI, Mapping of Breast Cancer: Department of Science and Technology, Government of India; Financial Interests, Institutional, Local PI, Protocol No. - ECTS/16/002 : A multicentric open label phase II safety and efficacy study of ormeloxifene in tamoxifen resistant metastatic/recurrent breast cancer patients.: HLL Lifecare Limited (A Government of India Enterprises); Financial Interests, Institutional, Coordinating PI, Protocol No. - D0818R0000 : Protocol no. D0818R00001- A Non-interventional, multicentre study to assess prevalence of BRCA1 and BRCA2 mutation among ovarian, primary peritoneal and fallopian tube cancer patients in India (BRCA study): AstraZeneca Pharma India Ltd.; Financial Interests, Institutional, Local PI, Protocol No. - 1000-16 : An Open Label, Single Arm, Multicentric, Phase IV study to evaluate the safety and efficacy of Bevacizumab of Intas Pharmaceuticals Limited in approved indications: Intas Pharmaceuticals Ltd; Financial Interests, Institutional, Local PI, Protocol No. - Protocol no: 471-13 : “A Prospective, Adaptive, Randomized, Open-Label, Multicenter Clinical Trial to assess the Efficacy and Safety of Fixed Dose Combination of Capecitabine & Cyclophosphamide in Patients of Metastatic Breast Cancer with failure of Anthracycline and/or Taxane Chemotherapy: Intas Pharmaceuticals Ltd; Financial Interests, Institutional, Local PI, Protocol No. - MO39196: A phase III, Multicentre, randomised, double-blind, placebo controlled study of Atezolizumab ( anti-PD-L1 antibody) in combination with paclitaxel compared with placebo in combination with paclitaxel for patients with previously untreated, inoperable locally advanced or metastatic Triple Negative Breast Cancer.: Roche Products (India) Pvt. Ltd; Financial Interests, Institutional, Local PI, Protocol No. - CBYL719C2301 : A phase III randomized double-blind, placebo controlled study of alpelisib (BYL719) in combination with fulvestrant for men and postmenopausal women with hormone receptor positive, HER2-negative advanced breast cancer which progressed on or after aromatase inhibitor treatment: Novartis Healthcare Pvt. Ltd.; Non-Financial Interests, Member of Board of Directors, This is a not-for-profit registered organization which aims to create large databases of genomic and other 'omic' data in breast and other cancers.: Indian Cancer Genome Atlas; Non-Financial Interests, Leadership Role, General Secretary of this non-governmental organization (It is a not-for-profit) which aims to help underprivileged patients with breast and gynecological cancers and promotes research and educational activities in these themes.: Women's Cancer Initiative - Tata Memorial Hospital; Non-Financial Interests, Leadership Role, President-Elect of ISMPO which is the largest professional organization of medical oncologists in India. It is a not-for-profit registered society.: Indian Society of Medical and Paediatric Oncology (ISMPO). All other authors have declared no conflicts of interest.