'Screen More' for Cancer Risk Genes

“Mutations in BRCA genes can give women up to an 80% chance of developing breast cancer.

“A trial involving 1,034 Ashkenazi Jews, who are at high risk, suggested more than half of their cases were not being picked up under the current NHS guidelines.

“The Eve Appeal charity said wider testing would save lives and money.

“Mutations in BRCA genes stop DNA repairing itself and increase the risk of cancer developing.

“As well as breast cancer, they are also linked to ovarian and prostate cancers.”

With Gene Mutations, Second Breast Cancer Risk Rises over Time

“Women who are genetically susceptible to breast cancer and develop it in one breast are at higher than average risk for a tumor in the other breast, and that risk may increase as time goes on, according to a new analysis.

“Mutations in the BRCA 1 or 2 genes increase the risk for several types of cancer and account for 5 percent to 10 percent of breast cancers, according to the National Cancer Institute.

“Researchers from Spain reviewed 20 studies of the risk of cancer in the second breast of BRCA 1 and 2 carriers.

“For breast cancer patients with the BRCA 1 mutation, the risk of a cancer in the opposite breast rose from 15 percent at five years after diagnosis to 27 percent at 10 years and 33 percent at 15 years.

“For the BRCA 2 mutation, the risk increased from nine percent at five years to 19 percent at 10 years to 23 percent at 15 years.

“For women with neither mutation, the risk of cancer in the opposite breast stayed low at 3 percent and 5 percent at the five and 10 year marks, according to results in the journal The Breast. There wasn’t enough data to estimate the 15-year risk in this group, the authors write.”

Genetic Testing Could Improve Breast Cancer Prevention

“Scientists used mathematical models to show that analysing genetic data, alongside a range of other risk factors, could substantially improve the ability to flag up women at highest risk of developing breast cancer.

“Their study showed that prevention strategies could be improved by testing not only as currently for major cancer predisposition genes such as BRCA1 and BRCA2 – which identify a small percentage of women at very high risk – but also by factoring in data on multiple gene variants that individually have only a small effect on risk, but are more common in the population.

“The research was carried out by researchers at The Institute of Cancer Research, London, and the National Cancer Institute in Bethesda, US – and is published today (Thursday) in the Journal of the National Cancer Institute.

“The study received funding from The Institute of Cancer Research (ICR), Breakthrough Breast Cancer and the National Cancer Institute.

“Researchers stressed that their study was a computer modelling analysis and would need to be confirmed by further research aimed at validating the models they used and assessing real-life prevention approaches.”

Olaparib Shows Success in Tumor Response Rate for Patients with BRCA-Related Cancers

The gist: A drug called olaparib has shown promise for treating people with breast, prostate, ovarian, and pancreatic cancers. In a clinical trial with volunteer patients, olaparib was shown to shrink tumors or make them disappear in 26 percent of the patients. All patients involved had inherited BRCA1 or BRCA2 mutations.

“Olaparib, an experimental twice-daily oral cancer drug, produces an overall tumor response rate of 26 percent in several advanced cancers associated with BRCA1 and BRCA2 mutations, according to new research co-led by the Abramson Cancer Center of the University of Pennsylvania. The positive response provides new hope for patients with ovarian, breast, pancreatic and prostate cancers whose conditions have not responded to standard therapies. Results of the phase II study are available online in the current issue of the Journal of Clinical Oncology.

“For the majority of patients in the study, olaparib was at least their third different cancer therapy. Based on the new data, the authors say olaparib warrants further investigation in phase III trials. The positive response in metastatic pancreatic cancer patients who had received an average of two prior rounds of chemotherapy is an especially noteworthy finding since therapeutic options for these patients are limited.

“The international research team studied nearly 300 patients with inherited BRCA1 and BRCA2 mutations who had advanced cancers that were still growing despite standard treatments. Patients were enrolled and treated at 13 centers around the world. In addition to the 26 overall shrinkage or disappearance rate in tumors following treatment with olaparib, researchers also found no further growth in cancer for at least eight weeks in 42 percent of patients.”

Newer Tests Clarify Hereditary Risk of Cancer

“Patients who years ago breathed a sigh of relief because their genetic tests showed they were not at increased risk of developing cancer are not necessarily home free, said Suzanne Mahon, DNSc, genetic counselor for Saint Louis University Cancer Center.

” ‘There is this group of people who think they don’t need to worry about getting cancer and believe they don’t have a high family risk of getting cancer, but unfortunately do,’ said Mahon, a professor in internal medicine at Saint Louis University.

“Mahon says her requests for genetic testing for breast cancer have more than tripled since 2013, when actress Angelina Jolie announced she had a double mastectomy because she was at genetic risk of developing breast cancer.

“Older genetic screenings were for the BRCA 1 and 2 genes, which are linked to the development of breast, ovarian, prostate, melanoma, pancreatic and other cancers.

“However a new generation of genetic tests can detect as many as 25 other, less common genes that show a familial predisposition to cancer.”

BRCA Mutation Incidence Comparable Between ER-Negative, ER-Low–Positive Breast Tumors

The gist: Researchers say that breast cancer patients younger than 60 who have ER-low-positive tumors should be “referred for genetic counseling and BRCA testing.” This is because a BRCA1 or BRCA2 mutation may affect treatment choices.

“The rate of deleterious BRCA1 or BRCA2 germline mutations detected in patients with ER-low–positive breast cancer is similar to that observed in patients with ER-negative breast cancer, according to study results presented at the Breast Cancer Symposium.

“The findings suggest the potential for underutilization of BRCA testing among appropriate patients, researchers wrote.

“ ‘In light of the life-saving interventions that may be offered to a patient once he or she has been identified to carry a deleterious BRCA mutation, we strongly recommend patients younger than age 60 with ER-low–positive tumors be referred for genetic counseling and consideration of BRCA testing,’ Rachel A. Sanford, MD, a fellow in cancer medicine at The University of Texas MD Anderson Cancer Center, said during a presentation.”

Lasker Award-Winner Urges Wider Genetic Tests for Cancer

“An American scientist Monday was awarded a top prize for discovering the location of the BRCA1 gene for breast cancer, and used the occasion to call for wider genetic testing of women.

“Mary-Claire King was given the Lasker-Koshland Special Achievement Award in Medical Science for her lifetime of work. The award is among the top honors in the field of science, and is often called the “American Nobel.”

“In an article published in the Journal of the American Medical Association to coincide with the award, King said more genetic testing should be done to catch inherited cancers before it is too late.

” ‘Based on our 20 years’ experience working with families with cancer-predisposing mutations in BRCA1 and BRCA2, it is time to offer genetic screening of these genes to every woman, at about age 30, in the course of routine medical care,’ she wrote.

” ‘To identify a woman as a carrier only after she develops cancer is a failure of cancer prevention,’ said King, a professor of genome sciences at the University of Washington School of Medicine in Seattle.”

Study of Jewish Women Shows Link to Cancer Without Family History

“Women of Ashkenazi Jewish descent who tested positive for cancer-causing genetic mutations during random screenings have high rates of breast and ovarian cancer even when they have no family history of the disease, researchers reported Thursday.

“The finding calls into question the practice of screening women — particularly women of Ashkenazi descent, as are most Jews in the United States — for these mutations only if they report that many women in their family have had cancer. Some women are tested for mutations only after they develop cancer themselves.

“Many of the women identified by the researchers in Israel would never have known they were mutation carriers if not for the screening offered by the study, the researchers said. The study’s authors recommended routine screening of all women of Ashkenazi backgrounds for harmful mutations in the genes, called BRCA1 and BRCA2.”

BRCA2 Mutations Herald Poor Prognosis in Screen-Detected Prostate Cancer

Editor’s note: You may have heard about the BRCA2 mutation, which can increase a person’s risk for breast cancer. Studies have also shown that it can increase a man’s risk of prostate cancer. Studies have also shown that prostate cancer patients with BRCA2 mutations generally do not survive as long as prostate cancer patients without BRCA2 mutations. A new study explored this more in depth by looking at survival rates for BRCA2+ men who were diagnosed with prostate cancer after standard screening. These men did indeed have shorter survival times than prostate cancer patients without BRCA2 mutations. The researchers say these patients might “benefit from additional therapies, such as with cis-platinum or a PARP [poly ADP-ribose polymerase] inhibitor.”

“Among men with prostate cancer detected on screening, survival among those with a mutation in the BRCA2 gene is much poorer than in those without such a mutation, researchers report.

“The findings suggest that BRCA2 mutation carriers may warrant additional treatments to improve their prognosis, say Steven Narod (Women’s College Hospital, Toronto, Ontario) and fellow authors writing in the British Journal of Cancer.

“BRCA2 mutations are known to confer an increased risk for developing prostate cancer and also to be associated with more aggressive tumours. However, the effect of BRCA2 mutations status on mortality in the setting of screen-detected cancers is unclear.”