N Engl J Med 2015 Jan 8
Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer.
Abstract
Background
No single standard treatment exists for patients with small, node-negative, human epidermal growth factor receptor type 2 (HER2)-positive breast cancers, because most of these patients have been ineligible for the pivotal trials of adjuvant trastuzumab.
Methods
We performed an uncontrolled, single-group, multicenter, investigator-initiated study of adjuvant paclitaxel and trastuzumab in 406 patients with tumors measuring up to 3 cm in greatest dimension. Patients received weekly treatment with paclitaxel and trastuzumab for 12 weeks, followed by 9 months of trastuzumab monotherapy. The primary end point was survival free from invasive disease.
Results
The median follow-up period was 4.0 years. The 3-year rate of survival free from invasive disease was 98.7% (95% confidence interval [CI], 97.6 to 99.8). Among the 12 relapses seen, 2 were due to distant metastatic breast cancer. Excluding contralateral HER2-negative breast cancers and nonbreast cancers, 7 disease-specific events were noted. A total of 13 patients (3.2%; 95% CI, 1.7 to 5.4) reported at least one episode of grade 3 neuropathy, and 2 had symptomatic congestive heart failure (0.5%; 95% CI, 0.1 to 1.8), both of whom had normalization of the left ventricular ejection fraction after discontinuation of trastuzumab. A total of 13 patients had significant asymptomatic declines in ejection fraction (3.2%; 95% CI, 1.7 to 5.4), as defined by the study, but 11 of these patients were able to resume trastuzumab therapy after a brief interruption.
Conclusions
Among women with predominantly stage I HER2-positive breast cancer, treatment with adjuvant paclitaxel plus trastuzumab was associated with a risk of early recurrence of about 2%; 6% of patients withdrew from the study because of protocol-specified adverse events. (Funded by Genentech; ClinicalTrials.gov number, NCT00542451.).
Related Questions
What is your treatment approach in a patient with cT2 ER+HER2+ breast cancer who refuses neoadjuvant chemotherapy?
Standard neo-adjuvant chemotherapy that contains trastuzumab, pertuzumab carboplatin, and docetaxel is recommended for most cases of HER2+ breast cancer (although other, anthracycline-containing regimens also exist but are used increasingly less commonly). If this patient refuses neo-adjuvant chemot...
What treatment would you provide for a patient with bilateral synchronous locally advanced cT4dN0 TNBC and cT1b ER+ HER2+ breast cancer?
Yes, the TNBC seems to be locally advanced and being T4d, would qualify for the KEYNOTE-522 regimen. The HER-2 positive cancer is small and clinically lymph node negative, so upfront surgery followed by adjuvant anti HER-2 therapy based on APT trial would be reasonable. But since the patient would h...
What adjuvant systemic therapy would you recommend for a woman s/p ALND for a nodal recurrence of ER-/HER2+ breast cancer 1 year after completing adjuvant therapy with paclitaxel/trastuzumab for her initial disease?
If the axillary nodes were already dissected, I would try TCHP followed by HP since she is pertuzumab naive and she had a DFI of >12 months from paclitaxel. If she had her nodes clipped for neoadjuvant TCHP, I would have switched to adjuvant TDM1 if she had residual disease in the axillary nodes.
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For a post-menopausal woman with a pT1c node negative HER2 positive breast cancer, does ER status influence your choice of adjuvant paclitaxel/trastuzumab versus docetaxel/carboplatin/trastuzumab?
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In patients with stage II-III HER2+ breast cancer who were not treated with neoadjuvant therapy, without having knowledge of response to neoadjuvant therapy (i.e. pCR or not) after chemotherapy, what is your preferred adjuvant HER2 directed therapy?
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What would you offer as systemic therapy to an elderly woman (age >75 years) with HR negative, HER2 positive, lymph node negative breast cancer whose tumor is 2 cm or less?
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Can paclitaxel and trastuzumab be given neoadjuvantly in Her2 positive breast cancer?
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Would you use single agent adjuvant HER2 directed therapy for patients with low risk HER2+ breast cancer who are not candidates for chemotherapy?
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