Tag Archive for: breastcancer

Some driver RET mutations are not observed in Indian cancers

The impact of two driver mutations of RET gene, V804M/L and S891A, on Thyroid cancer was described recently by Pichardo et al in JAMA Otolaryngology, 2023. In a population screening, 75 people were identified to have 2 Pathogenic or Likely Pathogenic (P/LP) germline variants of the RET gene. 20 out of these 75 patients chose to undergo prophylactic thyroidectomy even though they did not have any symptoms of cancer. After surgery, pathological analysis of their tissue detected the growth of medullary or papillary thyroid cancer (PTC) in 12 and 2 patients respectively, i.e., 70% of patients with these 2 mutations had been harboring cancer unknowingly!
We examined the presence of these 2 RET variants in Sapien’s 61 Indian thyroid cancer samples profiled in the OncoMineDx panel by ThermoFisher. P/LP mutations were seen in 4 cases, all below the age of 40. Three cases were PTCs and 1 Follicular, with an overall percentage of 6%. The variants detected were V804M/L (3 cases) and C618Y (1 case, Follicular). No case of S891A mutation was detected.
We also checked for RET mutations in our genetically profiled lung cancers (103 cases) where 28 cases had SNVs with 5 cases of V804M, and 1 case had a fusion. No case of S891A was observed. Similarly, among 449 breast cancers, 280 CRCs, 47 gliomas and few cases each of endometrium, urinary bladder and prostate cancers that have been genetically profiled, many cases of V804M/L and other P/LP RET mutations were observed but none of S891A.

HER2 Oncogenic mutations and amplifications are common across many Indian solid tumors

Until recently, HER2 (or ErbB2) targeting drugs were only approved for HER2-amplified breast & gastric cancers. FDA has now granted accelerated approval for trastuzumab or Enhertu to treat lung cancer patients bearing activating HER2 mutations. We analyzed our data of ~1000 solid cancer cases generated using the OncomineTM Dx NGS panel to determine the pattern of ERBB2 amplification vs. mutations. We see that in some cancers, amplifications are more common (breast, gastric, endometrial cancers) but in others, activating mutations are more common (colorectal, lung, thyroid and gliomas) with the most common mutation being V842I in Indian samples. Molecular insights gained from such NGS analysis can hopefully improve precision medicine by expanding the use of approved HER2-targeting drugs for colorectal, endometrial, gliomas, thyroid and other cancer patients that are likely to benefit from them.

KRAS mutations in Breast cancer may be treatable

For decades, mutations in #KRAS have been known to cause cancers in multiple organs and the gene KRAS itself was considered ‘undruggable’. Of the many mutations, KRAS-G12C is known to occur in nearly 13% of #NSCLC cases. There were no known treatments that can target KRAS-G12C mutation until recently. May 2021 heralded the #fdaapproval of Sotorasib, granted to #amgen, for treatment of #lungcancer with the G12C mutation in KRAS. Exciting results showed a reduction in tumour burden in more than 37% of the trial participants. This paves the way for testing the efficacy of the drug in multiple other cancers harbouring this driver mutation.
Our data identified nearly 7.8% of breast cancer #FFPE samples bearing the KRAS-G12C mutation, bringing hope of this #drug to people with #breastcancer.

The largest category of breast cancers are hormone receptor (HR) positive. These comprise 55-60% of all breast cancers globally as well as in India. Unlike triple negative breast cancer (TNBC), HR positive breast cancers respond well to personalized treatment with newer drugs and have a high chance of successful treatment and long-term survival even in advanced stages. Hence it is important to get them diagnosed and typed for HR positivity early on and tailor the treatment for each patient.

Breast Cancer Protection,

The Forum for Breast Cancer Protection, an NGO co-founded by caring oncologists and clinicians such as the inspiring, untiring Dr. Ramesh Sarin who continues to operate at the young age of 80 and give excellent care to her breast cancer patients. Col Pant, Dr. Sangeeta Taneja, @Karuna Sharma, Dipali Bhasin are catalysts that are active in organizing informative webinars and awareness sessions. This one on the 12th October was particularly memorable in that Ms. Sonam Kalra, a renowned singer, spoke of her mother who was diagnosed of lung cancer at the most advanced stage. She was given 6 months to live, but through her positive attitude, good routine and food, family and medical support, she lived life for 8 years, composing haikus till the end! Sonam spoke movingly of her mother and her determination to fight cancer. Her mother coined the term Cancer Samurai. Sonam sang ‘ek naam, satnam’ so beautifully it gave us goosebumps. What a treat. Then came the advice on how to use affirmation and visualization to think positively to heal our body and mind by Shivani ji, sage words in her soothing voice. Close your eyes, just listen, and feel the stress fade away.

Breast cancer remains a significant societal, clinical and scientific challenge. It is very crucial to understand the epidemiology, epi/genetics, molecular pathology, cell and protein biology and the influence of hormones on its development and progression. Breast cancer remains the leading cancer in Indian women and worldwide hence raising awareness for risk factors and early detection is critical to increase the quantity and quality of life.

Sree Voleti of BioNest and UoH in a wide-ranging frank monsoon chat with Jugnu on why she chose to return to India, why an entrepreneur, why Sapien, why Apollo, why Hyderabad …. on the road less travelled