Breast Cancer in India: A call for genetic equity

Ranjani Ramamurthy

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llmed.ai

6 min readAug 24, 2023

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Best wishes and gratitude to Dr. Suveera Dhup and Dr. Anand Deshpande who’re spearheading the creation of ICGA, the Indian Cancer Genome Atlas.

Breast cancer is the mostly commonly diagnosed cancer amongst women in the US and many of us know a friend/family member affected by the disease. Recently, I’ve met many women of Indian origin (both here in the US and in India) who have been affected by the disease.

Some of these women (in the US) had a known family history of breast and ovarian cancer and had unknowingly trusted direct-to-consumer (DTC) genetic tests (like 23AndMe) for their cancer susceptibility. They did not know that these tests did not test for genes/variants specific to their Indian ancestry. A few of these women continued with their normal annual mammograms and were sadly caught unawares by a breast cancer/ ovarian cancer diagnosis. Had their genetic predisposition to these cancers been highlighted earlier, these women could have been more intensively screened and could have been given options to reduce risk.

These conversations got me on an information-gathering mission on how breast cancer affects women of Indian origin both for those living in India and abroad. I’ve dug into the literature and spoken with patients of Indian-origin both in the US and in India. I’ve also talked to practicing oncologists in India as well as leaders in India, in philanthropy and medicine who’re trying to advance the science and care for women of Indian origin.

Learnings to share:

About the cancer:

Breast cancer in India is a disease of younger women, presenting at reproductive age as compared to the west (30s/40s vs. 60s).
In fact ~50% of breast cancer is diagnosed in women under the age of 50.
It is the most diagnosed cancer In India, surpassing both cervical and lung cancer.
Breast cancer is diagnosed at later stages. more often of the triple-negative kind (aggressive and harder to treat), and has lower survival rates than in the west.
The burden of the disease is expected to increase substantially over the next few decades.

Genomic makeup:

India is a heterogenous country with significant differences in genomic makeup in geographic regions. Genomic variants are different between sub-groups within a region.
Due to the lack of representation in global genetic databases (Indian genomes estimated at 0.2%), not much is known about the genetic variants particular to Indian populations for breast cancer.
Women who do get diagnosed tend to fare poorly on standard protocols developed for the western population.
Failure of therapy is a failure of accurate genetic characterization of the disease.

Enabling research for Indian women:

To understand the genetic characterization of the disease, we need a breast cancer specific biobank.
A biobank with linked clinical information is the best way to prospectively collect a hypothesis free and clean dataset.
Collecting biological samples, linked clinical correlates, sequencing and constructing scientifically sound insights on variants specific to sub-groups in India, will be a daunting task.
A plan will have to take into account the scientific, financial and logistical challenges of executing on this vision in a large, diverse country where there are many competing demands for resources. Cultural, societal and socieoeconomic factors will play an equally significant role.
The ICGA (modeled on TCGA, in the US) is in the early stages of building a biobank for India. I am optimistic that in time the data it collects, and the research that it enables will help better characterize disease in Indian women and pave a path to therapeutics and protocols tailored to the population.

Breast Cancer: A concern for women of reproductive age

Breast cancer is a disease of younger women of reproductive age in India, surpassing cervical cancer as the most diagnosed cancer amongst women.

All data/visuals from the WHO’s GLOBACAN website.

Women are diagnosed at an earlier age, later stage at presentation and more often, present with triple-negative breast cancer (25–33% higher than in the west). They also have delays in accessing treatment and frequently have inadequate and fragmented care. Cost of care is a concern as well.

While incidence rates of breast cancer in India are lower than in the west, survival rates are also much lower. In fact, the median survival 5 years after treatment, is < 60% ( as compared to > 80% in the west). These factors makes India the home of most of the world’s “cancer orphans”.

Note that by 2040, incidence is expected to increase by 30.4% and mortality by 32.9% to levels in 2020. This is for Indian women between the ages of 20–54.

Estimated Incidence/Mortality in India, for Breast Cancer, 2020–2040, Females 20–54

India’s unique genetic makeup:

India has a very heterogenous population. Ancient migrations as well as cultural and societal norms (like endogamy — i.e. marrying within a community) have contributed to the unique genetic makeup of sub-groups within the population.

There is currently no national biobank for breast cancer. Literature is usually based on patients at a single center. A study at a North Indian tertiary care center found that Indian patients presented with more pathogenic and different mutations than reported in studies based on western populations. Mutations were present on non-BRCA genes as well. That same study also found that genetic testing for Indians needs a re-think given that some of the preliminary screening methods (developed in the west) are not as relevant to the Indian population.

Other studies (here, here) echo similar findings with a call to genomically characterize breast cancer as it is experienced by Indian women.

The need for a national biobank:

Cancer is a genetic disease. While each patient has a unique genomic profile, discovering and sudying variants unique to a population (including sub-groups within the population), and linking that information with clinical correlates will go a long way toward understanding the risk factors, development of polygenic risk scores, understand the presentation, progression of the disease as well as response to therapy.

Studying breast cancer genetics requires data. It requires deep genomics and longitudinal clinical data collected at a national level. The data needs to be collected at diagnosis and at various inflection points in the treatment journey. The data then needs to be analyzed with modern bioinformatics methods with an understanding of the nuances of the ethnic diversity of India.

The ICGA is in the very early stages of building a national biobank for breast cancer in India. But it needs visibility, support, and a global understanding of the importance of this investment. After all, this will positively affect the health of 20% of the world’s women!

Executing on building a national biobank where all regions and ethnicites are represented will be a mammoth task : financial, logistical, operational and technical.

But somehow, I think that a country that has beat polio can do this!

References:

Breast Cancer in India: A call for genetic equity

Written by Ranjani Ramamurthy