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More Support for Genetic Testing in Breast Cancer

MIAMI BEACH — An integrated genetic testing program identified pathogenic variants in 10% of tested patients in a comprehensive breast cancer program, as reported here at the Miami Breast Cancer Conference (MBCC).

Some patients had positive tests as much as 10 years after their initial diagnosis. All patients with positive tests had consultations with a physician or advanced practice provider and offered referral to a genetic counselor and to resources for cascade testing.

“Genetic testing is a necessary step to stratify a breast cancer survivor’s risk of developing secondary cancers, appropriate screening and prevention strategies, cascade testing, and for some, treatment planning,” concluded Lori Ranallo, ARNP, of the University of Kansas Cancer Center in Kansas City, Kansas, and colleagues. “This individualized approach to breast cancer survivorship care is often described … but difficult to put into action.

“Time/access and drop rates with a referral model are barriers. Incorporating a point of care genetic testing model requires additional support … professional development, education, and a commitment to provide patient-centric care.”

The report, voted the best poster abstract submitted to MBCC, described results of the testing program in 1,845 breast cancer survivors seen at the cancer center from May through December 2019. The time since breast cancer diagnosis averaged 10.7 years. A total of 201 (10.9%) of patients had undergone genetic testing, including update (3%) and initial (7.8%) testing. A positive family history was the indication for testing in 89.5% of cases. In 96% of cases, patients had no out-of-pocket costs for testing, and the cost averaged $206.22 for the remaining 4% of patients.

Results reported in another poster presentation suggested that combined testing for germline and somatic mutations in breast and ovarian cancer would aid clinical decision-making and management and be more efficient.

The study involved 257 patients with a diagnosis or history of breast or ovarian cancer, a referral for germline testing, and prior tumor DNA sequencing. Common reasons for referral included a somatic finding with potential germline significance, treatment/surgical planning, persona/family history, and patient concern, reported Stephen E. Lincoln and colleagues of Invitae in South San Francisco, California.

In addition to the somatic mutations, 100 (39%) patients harbored a pathogenic germline variants in a cancer predisposition gene. In 9% of cases, germline mutations were not reported as part of tumor test results. A majority of the pathogenic variants were actionable by current treatment guidelines, labeling of approved therapies, or clinical trial eligibility. The investigators found that 29% of germline mutations were identified only after patients were evaluated for a second, potentially preventable cancer.

“At a minimum, our study demonstrates that reflex germline testing following tumor testing can significantly impact management,” the investigators concluded. “As an alternative, upfront paired germline and tumor testing would have the added advantages of integrated results and shorter turnaround time. Both approaches remain underutilized.”

In other MBCC presentations, more than 40% of patients with HER2-positive breast cancer and brain metastases responded to neratinib (Nerlynx)-containing regimens across three different clinical trials.

In the largest of the three cohorts, 18 of 37 (48.6%) patients with central nervous system (CNS) lesions responded to neratinib and capecitabine. Data from a cohort of 32 randomized patients with CNS lesions showed objective responses in five of 19 (26.3%) patients treated with neratinib and capecitabine versus two of 13 (15.4%) patients who received lapatinib (Tykerb) and capecitabine.

The third cohort comprised a total of six patients from a randomized trial pairing paclitaxel with neratinib or trastuzumab (Herceptin). All three patients randomized to neratinib had objective responses compared with one of three randomized to trastuzumab.

Overall, 26 of 59 (44.1%) patients with CNS involvement responded to a neratinib-containing regimen. Patients who achieved objective responses had longer progression-free survival (11.3 months vs 5.6 months, P=0.087) and overall survival (27.1 vs 11.5 months (HR 0.43, 95% CI 0.24-0.76, P=0.003), reported Sara Hurvitz, MD, of the University of California Los Angeles, and colleagues.

A subgroup analysis of an ongoing trial showed that ribociclib (Kisqali) and letrozole led to similar objective response and clinical benefit rates (ORR, CBR) regardless of CNS involvement in patients with hormone receptor (HR)-positive/HER2-negative breast cancer.

The analysis focused on 50 patients with CNS metastases in the single-arm phase IIIb CompLEEment-1 trial, which involved a total of 3,246 patients. The data showed an ORR of 41.2% in patients with CNS lesions and 30.9% in those without. CBR was 61.8% and 64.2% in patients with and without CNS involvement. The 50-patient subgroup had a median time to progression of 16 months and an estimated 12-month event-free survival of 72.5%, reported Paul Cottu, MD, of the Institut Curie in Paris, and colleagues.

Last Updated March 09, 2020


Renallo and co-authors disclosed no relevant relationships with industry.

Lincoln and co-authors are employees of Invitae.

The neratinib studies were supported by Puma Biotechnology, the Translational Breast Cancer Research Consortium, Breast Cancer Rsearch Foundation, and Susan G. Komen. Hurvitz disclosed relevant relationships with Ambrx, Amgen, Arvinas, Bayer, Cascadian Therapeutics, Daiichi Sankyo, Dignitana, Genentech, GlaxoSmithKline, Eli Lilly, MacroGenics, Medivation, Merrimack Pharmaceuticals, Novartis, OBI Pharma, Pfizer, Pieris Pharmaceuticals, Puma Biotechnology, Radius, Roche, Seattle Genetics, and Immunomedics.

The CompLEEment-1 trial was supported by Novartis. Cottu disclosed no relevant relationships with industry. Co-authors disclosed relevant relationships with Novartis, Pfizer, Roche, Celgene, AstraZeneca, Eli Lilly, Amgen, Bristol-Myers Squibb, Incyte, Molteni, Merck Sharp and Dohme, Janssen, Fondazione Medicina Personalizzata, and Teva.