榴莲视频

Adding trastuzumab (Herceptin) to adjuvant chemotherapy didn't cause long-term deterioration of cardiac function, cardiac symptoms, or health-related quality of life (QoL) in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, a study showed.

Five (4.5%) of 110 women in the control group and 10 (3.4%) in the trastuzumab group had a more than 10% decline in left ventricular ejection fraction (LVEF) from baseline to a value less than 50% in the Protocol B-31 long-term cardiac follow-up study of women from the National Surgical Adjuvant Breast and Bowel Project (NSABP).

Fully 95.3% of the 297 patients with no underlying cardiac disease at baseline randomly assigned to receive trastuzumab had LVEF of at least 50% after a median of 8.8 years. Only two (0.6%) patients in the trastuzumab group had LVEF ≤40%, Patricia Ganz, MD, of the University of California Los Angeles and colleagues reported online in the .

"Our report provides encouraging data from the B-31 study and indicates that in breast cancer survivors without a pre-existing cardiac history, the addition of trastuzumab to adjuvant anthracycline-based chemotherapy does not result in long-term worsening of cardiac function, cardiac symptoms, or HR-QoL [health-related quality of life]," the study authors wrote. "These results are consistent with that the cardiac effects of trastuzumab are generally reversible and qualitatively different from anthracycline-induced cardiomyopathy."

Long-term follow-up of patients who remained cancer-free after adjuvant therapy also showed that low scores on patient-reported outcomes using the Duke Activity Status Index (DASI) correlated with age, hypertension medication use, cardiac conditions, diabetes, and hyperlipidemia but not with trastuzumab adjuvant therapy. Women with scores in the lowest tertile were more likely to require cardiac-related medications at long-term follow-up assessment, the study showed.

"We have also demonstrated the potential value of including PROs [patient reported outcomes] along with physiologic measures of cardiac function in follow-up of breast cancer survivors who have received cardiotoxic treatments," Ganz and colleagues wrote.

"The DASI questionnaire may provide a simple and useful tool for monitoring patient-reported changes that reflect cardiac function."

Prospective studies should evaluate whether the DASI questionnaire can identify functional declines that require formal assessment of cardiac function, they added.

Results from have raised concerns that in routine clinical practice, trastuzumab-related cardiac toxicity may be greater than that seen in clinical trials, even in older patients not treated with anthracyclines, the investigators pointed out. Long-term cardiac follow-up of women who survive without disease recurrence is important, because patients who remain cancer-free after completion of adjuvant treatment aren't followed with objective measures of cardiac function and QoL.

Of 2,119 patients enrolled in the who received anthracycline and taxane chemotherapy with or without trastuzumab, there were 963 eligible patients who were breast cancer-free after treatment ended. A total of 441 women were recruited from this group for the long-term follow-up study. Mean age was 58 years.

Assessment included measurement of LVEF by multigated acquisition scan, patient-reported outcomes using the DASI survey and the Medical Outcomes Study questionnaire, and a review of current medications and comorbid conditions.

"Our data suggest that there is no further deterioration in cardiac function attributable to trastuzumab beyond 18 months post initiation of treatment," Ganz told 榴莲视频. However, she added, the findings are limited by the fact that "not all eligible women participated in the follow-up study, and the B-31 patients were very young. So trials that may have included older patients may show different outcomes."

One of the biggest clinical takeaways from this study was that patients were able to report symptoms associated with an increased risk for heart problems by giving yes or no responses to the 12-item DASI questionnaire.

"Regularly asking patients these questions may detect worsening cardiac function, and this could trigger more detailed cardiac evaluation, for example, with an echocardiogram," Ganz explained, noting that this inexpensive approach may be more efficient than follow-up imaging at arbitrary intervals.

Patients receiving trastuzumab in a routine setting are likely to have more comorbid conditions than women in clinical trials such as the B-31, she pointed out. These patients may also be older. For these reasons, "careful monitoring with the DASI may alert clinicians to worsening cardiac function before patients get into trouble."

"Trastuzumab has proven to be a transformative drug in breast cancer, offering remarkable improvement in outcomes for women with HER2 positive breast cancers," Harold Burstein, MD, PhD, of the Dana-Farber Cancer Institute in Boston, told 榴莲视频.

Although trastuzumab has few short-term side effects, "there have been concerns about the risk of damage to the heart, which can happen in about 2% of women treated with this drug," said Burstein, an American Society of Clinical Oncology expert. HER2-positive breast cancers account for 15 to 20% of all breast cancers, he noted.

These data not only demonstrate the long-term safety of trastuzumab, they "should be very reassuring to women, who can be confident that trastuzumab treatment reduces their cancer risk without causing late, damaging effects to the heart," said Burstein.

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