Understanding Your Genes Can Improve Your Cancer Prognosis

April 20, 2021

With most cancers, earlier disease diagnosis can significantly improve a patient’s clinical outcome.  

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With most cancers, earlier disease diagnosis can significantly improve a patient’s clinical outcome. Cancers detected at an early stage are localized and haven’t yet metastasized to other parts of the body, typically making them easier to effectively treat.

While people inherently have different risks for developing cancer, due to various risk factors and common genetic variants (changes), a smaller percentage of the population actually harbors rarer hereditary cancer mutations (adverse genetic changes) that confer a significantly increased risk of developing certain cancers over the course of a person’s lifetime. People that are diagnosed with these mutations before developing cancer typically have a strong genetic risk for the disease, such as a strong family history of a certain type or types of cancer on one side of their family. Others, however, only learn of their hereditary cancer mutation after a cancer diagnosis.  

Genetic screening tests are much more routine and affordable than they were 10 to 15 years ago, increasing patient access to genetic screenings and the diagnosis of hereditary cancer mutations. However, increased genetic screening did not answer one fundamental question: Does advanced knowledge of a hereditary cancer mutation, before cancer ever develops, improve patient outcome? Fortunately, one group of researchers designed a retrospective breast cancer study to determine just that.

The research team performed their study, conducted in Israel, by collecting and analyzing de-identified data from breast cancer patients carrying a BRCA1 or BRCA2 gene mutation between 2005 and 2016. The group recently published their results in JAMA.1 Mutations in the BRCA1 and BRCA2 genes cause hereditary breast and ovarian cancer (HBOC) syndrome, which greatly increases an affected person’s risk of developing breast, ovarian and other types of cancer during their lifetime. Of the 105 breast cancer patients in the study, 42 patients were aware of their BRCA mutation prior to developing breast cancer (preDx group) and 63 found out about their BRCA mutation after developing breast cancer (postDx group). None of the preDx patients in the study elected to have a risk-reduction bilateral mastectomy prior to developing breast cancer.

The researchers obtained the demographic, clinical and pathological data from patient medical records as well as current patient vital status. The team then compared the preDx group to the postDx group to determine significant differences in the course or outcomes of their breast cancer diagnosis and treatments. In short, the results of the study were striking.

preDx patients were significantly more likely to be diagnosed by MRI with either a noninvasive or lower-stage invasive breast cancer compared to postDx patients. After controlling for variables such as socioeconomic index (SI), age, year at diagnosis, family history (FH) and BRCA1 vs. BRCA2 mutation, researchers found that awareness of a BRCA mutation after breast cancer diagnosis significantly predicted a later stage cancer at diagnosis.  Additionally, preDx patients had lower rates of axillary lymph node dissection (removal of lymph nodes in the arm), which is standard protocol for breast cancers that have spread to the lymph nodes.  preDx patients were also less likely to undergo chemotherapy compared to postDx patients and none of the preDx patients required neoadjuvant chemotherapy.  The researchers calculated that the likelihood of advanced clinical stage (determined from tests performed prior to surgery) breast cancer at diagnosis is 12.1 times higher in postDx patients than preDx patients.  Here, advanced stage cancers refer to stage II, III and IV breast cancers.

Perhaps most importantly, when the researchers compared the overall 5-year survival rates (percentage of patients that survive five years after diagnosis) between the two groups, preDx patients had an overall 5-year survival rate of 94%, whereas the postDx group was only 78%.  A total of 4.8% of the preDx and 25.4% of the postDx patients in the study had died.  After controlling for variables such as BRCA1 vs. BRCA2 mutation, SI, age, FH, and year at diagnosis, the rate that a preDX patient would die compared to a postDX patient is 0.16, meaning that preDx patients die at a much lower rate than postDx patients, simply due to the patients’ prior knowledge of their BRCA mutation before developing breast cancer.

There were some additional factors outside of the timing of a BRCA mutation diagnosis that influenced cancer survival, which the researchers controlled for in many of their study calculations. High SI, which breast cancer gene (BRCA1 or 2) a patient’s mutation was present in, and a patient’s age at diagnosis all influenced disease outcome. Interestingly, most preDx patients in the study chose bilateral mastectomy after developing breast cancer. It is also important to recognize, and the researchers point out, that the study size is small and thus may be prone to bias. Despite the small size of the study, the average age at breast cancer diagnosis was the same between preDx and postDx patients, and there were no significant differences in cancer characteristics between the groups, such as the grade or hormone receptor status of the tumors, suggesting there were no obvious sources of bias in the study. All patients were also given the same surveillance and prevention recommendations based on established guidelines to eliminate treatment bias.

The results of the study outlined here are clear and compelling: Patients that knew of their BRCA mutation before developing breast cancer had an earlier stage cancer at diagnosis, underwent less chemotherapy and axillary dissection, and survived longer than postDx patients. Today, comprehensive hereditary cancer screening tests, such as the ExpedioTM Hereditary Cancer Screening, identify mutations in many genes with a single patient DNA sample. The ExpedioTM screen analyzes 33 hereditary cancer genes, including BRCA1 and BRCA2, for mutations, providing invaluable cancer risk information for affected patients, their families and clinicians. To order the Kalios Genetics ExpedioTM Hereditary Cancer Screening, click here or contact us with any questions you may have regarding genetic screenings.


1Hadar, T., et al.  Presymptomatic awareness of germline pathogenic BRCA variants and associated outcomes in women with breast cancer.  JAMA.  July 9, 2020.