Journal Scan

BREAST-CANCER THERAPY — LOOKING BACK TO THE FUTURE*

Anne Moore, MD

ADJUVANT therapy for breast cancer-treatment after surgicalremoval of the tumor-is a major therapeutic advance thathas had a considerable effect on prolonging disease-freeand overall survival. Not all patients benefit from adjuvanttherapy, however, and certain types of adjuvant therapy arenot appropriate for some patients. For example, adjuvanttreatment with tamoxifen, a selective estrogen-receptormodulator, has improved the 15-year survival rate amongwomen with estrogen-receptor–positive breast cancer by31%, but it does not benefit women with estrogen-receptor-negative disease. Trastuzumab, a monoclonalantibody against the human epidermal growth factorreceptor type 2 (HER2), is associated with an improvementof approximately 50% in disease-free survival among the15 to 20% of women with HER2-positive disease.

In addition to these targeted approaches, adjuvantchemotherapy that includes alkylating agents, anti-metabolites, anthracyclines, and taxanes in variouscombinations has contributed to the overall improvementin outcomes among women with operable breast cancer.As compared with women with estrogen-receptor–positivedisease, women with estrogen-receptor–negative breastcancer benefit more from chemotherapy. A recentretrospective analysis of three trials by the Cancer andLeukemia Group B (CALGB) suggests very little overallbenefit of adjuvant chemotherapy for women withestrogen-receptor–positive breast cancer who receivedtamoxifen for 5 years after receiving chemotherapy.

Why should we spare our patients from paclitaxel? Thetoxicity profile of this drug is unique. Hypersensitivityreactions (including, rarely, anaphylaxis) occur during theinfusion of paclitaxel, despite premedication with

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corticosteroids. Such reactions were reported in 6% ofpatients in the CALGB 9344 trial. A transient symptomcomplex of myalgia, arthralgia, and neuralgia is commonwithin 2 to 3 days after the infusion. Neurotoxicity, thepredominant side effect, was reported in 18% of patientsin the CALGB 9344 trial. For some patients, numbnessand tingling in the hands and feet last for months or evenyears after treatment is completed.

Thirteen years have passed since the first patient wasenrolled in the CALGB 9344 trial. During this time,important changes in practice may have diminished thevalue of adding paclitaxel to chemotherapy for womenwith HER2-negative, estrogen-receptor–positive breastcancer. For instance, advances in adjuvant endocrinetherapy reduce the proportional benefit of adjuvantchemotherapy for women with estrogen-receptor–positive breast cancer. In postmenopausal women, theincorporation of an aromatase inhibitor (anastrozole,exemestane, or letrozole) into adjuvant therapy prolongsdisease-free survival more than does treatment withtamoxifen for 5 years.

Leaders of clinical trials should continue to lookbackward, when appropriate, for data such as thosepresented by Hayes et al. In looking to the future,correlative science must be incorporated into modernclinical trials in breast cancer. The days of “one size fitsall” therapy for patients with breast cancer are coming toan end.

*SOURCE INFORMATION: New England Journal ofMedicine, Volume 357:1547-1549 October 11, 2007 . Fromthe Division of Hematology–Oncology, Weill Cornell MedicalCollege, Cornell University Medical Center, New York.