Precision Medicine in Cancer: Germline Testing Post Diagnosis

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Holly Magliochetti

Genetics Institute of America

Genetics Institute of America (GIA) is a national laboratory dedicated to heightening the awareness of early intervention and genetic screening to promote the longevity and quality of life outcomes.  


Precision Medicine in Cancer:

Post-Diagnosis Impact of Germline Genetic Testing

Germline Testing
December 8, 2021

DELRAY BEACH, FL – A germline variation in a cancer predisposition gene can have drastic effects on treatment response and outcome for patients with a current or previous cancer diagnosis, regardless of the cancer site. A staggering number of germline variations are associated with many types of cancers, including breast, ovarian, colorectal, prostate, etc. Germline testing offers both doctor and patient a way to treat cancer in an individualized and precise manner that improves outcome, safety, and quality of life.

Based on current research, the most common gene variations found in population are within BRCA1/2 and those associated with Lynch Syndrome, “affecting approximately 1 in 279 and 1 in 400 Americans, respectively.”1 Women with a BRCA variation have an increased lifetime risk of around 70% for breast cancer and 40% for ovarian cancer, versus 13% for breast and 1.3% for ovarian in the general population. Upwards of 10% of men with prostate cancer have a BRCA variation, as well. Lynch Syndrome-associated variations elevate risk of certain cancers up to 70%, including endometrial, ovarian, and pancreatic.1

For many hereditary cancers, including BRCA-linked, knowledge of a pathogenic variation can inform prevention and screening strategies. More importantly, germline testing can guide treatment decisions and options for care in patients already diagnosed with cancer. With a more accurate risk assessment from a multi-gene panel, such as the Genetics Institute of America GIAnomicsTM Hereditary Cancer Test, doctors can adapt treatment strategies to specific germline variants and reduce the high morbidity and mortality of these patients.1

Heritable Cancers and Treatment Examples Based on Germline Variants
Breast Cancer

“An estimated 20% of patient [sic] with triple-negative breast cancer (TNBC) are BRCA mutation carriers, and 70% of breast cancers that develop in BRCA1 mutation carriers are triple negative.”1 TNBC patients with BRCA variations are excellent candidates for PARP inhibitor therapy, platinum derivatives and have a better response to carboplatin therapy.1 Having a germline variant, in BRCA or PALB2, could also affect surgical decisions, including whether or not to get a double mastectomy or undergo other surgeries, because of the increased risk of additional primary cancers.

Colorectal Cancer

Lynch syndrome and the associated-gene variants account for 3% of all colorectal patients. As a result of heightened risk for uterine, gastric, and ovarian cancers, the knowledge provided by germline testing can lead to earlier detection of other primary cancers.1

Ovarian Cancer

“More than 1 in 5 ovarian carcinomas are associated with germline mutations.”1 Some are attributed to genes, such as PALB2, RAD51C, TP53 and MSH6, while most, about 15%, are associated with BRCA1/2 variations. Ovarian cancer patients with germline variants tend to respond to treatment differently than patients without a known pathogenic variant, including being more sensitive to intraperitoneal chemotherapy and platinum therapy.1

Prostate Cancer

A study in JAMA Oncology found that “17% of men with prostate cancer [have] germline genetic mutations. BRCA variants accounted for more than 30% of the mutations, and a number of variants with known therapeutic implications (CHEK2, ATM, PALB2, MUTYH, etc.) were identified.”1 BRCA-associated prostate cancer has been shown to respond to PARP inhibitor treatment and seems to be more sensitive to the benefits of carboplatin-based chemotherapy compared to men without a BRCA variant.1 With continued research and clinical trials, doctors will be able to provide prostate cancer treatments that are individualized and inform patients about their increased risk for other primary cancers.’

Knowledge of germline mutations will increase preventative screening of cancer patients and can also, identify patients with contraindications to their treatment regimen. For example, “patients with Lynch syndrome with stage II MSI-H tumors do not benefit from fluorouracil adjuvant treatment therapy. In the case of breast cancer, patients who are not carriers of a BRCA1/2 mutation are suitable for accelerated partial breast irradiation.”1

With so many treatment options available for these heritable cancer types alone, cancer patients should be offered germline genetic testing, like Genetics Institute of America’s GIAnomicsTM Hereditary Cancer Test, before any major treatment decisions are made. Not offering this invaluable tool could restrict a patient’s access to the life-saving treatment they need to improve their health outcome.

  1. Owens K, Schlager L, Welcsh PL. The impact of germline testing for hereditary cancer postdiagnosis. Am J Manag Care. 2019;25(9 Spec No.):SP285-SP287.
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