ASCO Publishes Two Clinical Guidelines For Treating HER2-Positive Breast Cancer

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The American Society of Clinical Oncology published two clinical practice guidelines on treating women with advanced, HER2-positive breast cancer.

The first guideline lists appropriate systemic therapies for women newly-diagnosed with advanced disease and those whose early-stage disease progressed to advanced cancer. The second provides recommendations for treating brain metastases. Both guidelines were published in the Journal of Clinical Oncology.

The first guideline, Systemic Therapy for Patients with Advanced HER2-Positive Breast Cancer, involved a review of 19 phase III clinical trials on HER2-targeted therapies, which helped an expert panel make recommendations for three lines of therapy. The key recommendations of the guideline are:

For first-line therapy: a combination of chemotherapy, trastuzumab and pertuzumab. For select patients, such as those with contraindications and/or slow growing hormone receptor-positive cancer, hormonal therapy administered with or without either trastuzumab or lapatinib may be substituted for a chemotherapy-based HER2-targeted regimen because it may have fewer side effects.However, hormonal therapy is not appropriate for all patients with advanced, hormone receptor-positive breast cancer and it has not been associated with a survival benefit in this setting.

For second-line therapy: trastuzumab emtansine. For third-line line therapy and beyond, treatment depends on what patients have received in the first- and second-lines. Options may include trastuzumab emtansine, hormonal therapy or chemotherapy with tratuzumab and in some cases with lapatinib, the combination of trastuzumab and lapatinib, or pertuzumab-based regimen if the patient had not previously received pertuzumab.

The second clinical practice guideline provides consensus-based recommendations for use of local and systemic therapies in patients with HER2 positive breast cancer that has spread to the brain and is the first guideline specifically for patients with HER2-positive metastatic breast cancer.

The key recommendations of the second guideline, Recommendations on Disease Management for Patients with Advanced HER2-Positive Breast Cancer and Brain Metastases, are: for patients with favorable prognosis for survival, surgery and/or radiotherapy are recommended, depending on the size and number of metastases, resectability, and symptoms.

For patients with a poor prognosis for survival, options include surgery, whole brain radiation therapy and systemic therapies with some evidence of activity in the setting of brain metastases, such as lapatinib and capecitabine. Additional options include best supportive care, enrollment in a clinical trial, and/or palliative care.

Researchers Link Obesity with 34 Percent Higher Death Risk in Pre-Menopausal Women

Researchers found that obesity is associated with a 34 percent higher risk of deaths related to breast cancer in pre-menopausal women with estrogen receptor positive disease. Obesity had little effect in post-menopausal ER-positive disease or in ER-negative disease.

“Obesity substantially increases blood estrogen levels only in post-menopausal women, so we were surprised to find that obesity adversely impacted outcomes only in pre-menopausal women,” said Hongchao Pan, a researcher at the University of Oxford. “This means we don’t understand the main biological mechanisms by which obesity affects prognosis.”

The study examined the cases of 80,000 women with early breast cancer in 70 clinical trials. Researchers compared records from women who received the same treatment in the same clinical trial.

Body-mass index was used to define normal weight, overweight, and obesity (20-25, 25-30 and ≥30 kg/m2, respectively). To assess the independent effects of BMI on prognosis, the researchers adjusted the findings for tumor characteristics such as size and nodal spread, and for any differences in treatment.

Among the 20,000 pre-menopausal patients with ER-positive disease, the breast cancer mortality rate was one-third higher in obese women than in women of normal weight. This would, for example, change a 10-year breast cancer mortality risk of 15 percent into a 10-year risk of 20 percent.

In contrast, obesity had little effect on breast cancer outcome either among the 40,000 post-menopausal women with ER-positive disease or among the 20,000 with ER-negative disease. The study, funded by Cancer Research UK, the MRC and the British Heart Foundation, will be presented at the annual meeting of the American Society of Clinical Oncology in Chicago on May 31.

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