How next-generation sequencing could change cancer care.

found that risk of heart failure was highly increased over 5 years in those taking tras-tuzumab alone or with an anthracycline as adjuvant therapy, compared with those given chemotherapy or anthracyclines alone, with risk rising with age (JNCI, Sept. 5, 2012). Risk of anthracycline-associated cardiac problems among women younger than 65 years was similar to that seen in randomized clinical trials, but trastuzumab-associated risk was greater than reported previously. Most studies are done in the context of clinical trials, with patients selected for few comorbidities, and show fairly low rates of cardiotoxicity, about a 2% increase with anthracyclines, and 4% over 3–5 years adding trastuzumab, Bowles said. Her study indicates that damage increases in the last year, with no evidence of plateau , The risk of heart failure in women with nonmetastatic disease taking trastuzumab is equivalent to or greater than that reported by clinical trials, Geiger concurred. But a third study, a phase III 7-year follow up trial part of the National Surgical Adjuvant Breast and Bowel Project (B-31), analyzed a younger, healthier population. Center in Lexington, found that risk of cardiotoxicity increased only for those on trastuzumab or anthracyclines plus trastu-zumab, and late heart failure was uncommon (online Sept. 17, 2012, Journal of Clinical Oncology). Perez, an author, noted that the first two studies were retrospective, with limitations. " We don't see those high rates in our clinic, and we believe that the combination provides an edge for patients in survival and recurrence, " she said, adding that much more data are needed before one can change regimens from anthracycline to taxanes and that evaluation of ejection fraction should be done before starting therapy. Anthracyclines and trastuzumab act syner-gistically to damage the heart, but in different ways, and risk and damage from both may be modifiable. Type I damage from anthracyclines generally produces irreversible , dose-dependent death to heart muscle cells, which increases over time, taking months to years to manifest, but may be reversible when caught early. Risk factors for anthracycline damage include prior use of these drugs, hypertension, and age. Monitoring cardiac function before, during, and after anthracycline and/or tras-tuzumab helps physicians detect early damage , enabling regimen modifications—but this too is controversial, and practice varies widely, less so in patients with preexisting risk factors. Monitoring no-or low-risk patients after four to five cycles of doxorubicin treatment could help identify patients with asymptomatic decrease in systolic …