To treat or not to treat? When it comes to deciding whether adjuvant chemotherapy is the appropriate management choice for patients with HER2 positive, node-negative breast cancer less than 1 cm in size, the only sure thing is that there is no sure thing, and seemingly conflicting research data exacerbates the uncertainty.
A recent study demonstrated that patients who did not receive adjuvant chemotherapy or trastuzumab for node-negative, non-metastasized HER2 positive T1a (less than or equal to 0.1 cm to 0.5 cm) or T1b (greater than 0.5 cm to 1.0 cm) tumors were at greater risk for worse recurrence-free survival and worse distant recurrence-free survival than patients with hormone-receptor–positive disease.
This was especially true for those younger than age 35 years – and also was the case in similarly staged patients with triple-negative breast cancer, according to the report from the University of Texas M.D. Anderson Cancer Center in Houston.
The authors concluded that planning systemic treatment based on disease stage alone "appears to lead to worse outcomes," and that individualized treatment plans may be better informed by taking into account aggressive biological subtypes of small, node-negative breast cancers, as well as age at diagnosis (Clin. Breast Cancer. 2011 July 15 [doi: 10.1016/j.clbc.2011.05.002]).
While the findings of this retrospective, single-institution study validate the large body of evidence suggesting that younger patients with aggressive tumor subtypes have worse outcomes when not treated with adjuvant chemotherapy or trastuzumab (Herceptin), the authors do not recommend universal treatment of this patient population.
Rather, the results provide a strong argument for the inclusion of women with small tumors that have biologically aggressive traits in prospective clinical trials "to evaluate the extent of therapeutic benefits," they wrote. Further, patient age and disease subtype "should be considered when counseling patients about treatment interventions."
No Treatment Not Worse for Some
With the absolute benefits of treatment yet to be determined, investigators also are looking closely at the risks associated with skipping adjuvant treatment.
The findings of an observational cohort study presented at the annual meeting of the American Society of Clinical Oncology (ASCO) suggest that women with early HER2 positive T1aN0M0 breast cancers can safely do so because of the low distant recurrence rate observed in this patient subgroup. A higher rate was observed in those with T1bN0M0, indicating that adjuvant systemic therapy may be more relevant in this patient population.
The study assessed outcomes among 237 women with HER2-positive T1a (116 patients) or T1b (121 patients) tumors diagnosed between 2000 and 2006, all of whom had negative nodes and no metastases. Most did not receive adjuvant chemotherapy or trastuzumab.
With a median duration of follow-up of 5.8 years, the rate of distant recurrence was 0.9% among patients with T1a tumors versus 5.8% among those with T1b, lead investigator Dr. Louis Fehrenbacher, an oncologist with Kaiser Permanente in Vallejo, Calif., reported in a poster presentation, analyzing data from the tumor registry of the Kaiser Permanente Clinical Care Program of Northern California.
Dr. Louis Fehrenbacher
The investigators chose distant recurrence-free survival as the main outcome measure, rather than the more commonly used disease-free survival rate, because they "did not want to include non-breast malignancies, contralateral malignancies, or deaths from any other cause," Dr. Fehrenbacher said. "That isn’t the real important factor in deciding to give intensive chemotherapy to these patients," he explained.
By tumor size, the rate of distant recurrence ranged from 0% to 5.8% for tumors measuring 0.1 cm to 0.9 cm, but it was 10.7% for the tumors measuring 1.0 cm. In other words, Dr. Fehrenbacher said, "the 1.0-cm tumors carried the burden of the distant recurrence risk."
Results for the actuarial distant recurrence-free interval showed a 5-year rate of 96.5% for the patients as a whole, with 99.1% and 94.0% in the T1a and T1b groups, respectively.
Overall, 25% of the study patients received chemotherapy and 8% received trastuzumab. "Most of these patients had only a smattering of chemotherapy or trastuzumab, and it didn't seem to affect outcome," Dr. Fehrenbacher commented, but he acknowledged that there may have been bias influencing who received chemotherapy. While 59% of the patients had tumors that were positive for estrogen receptors, there was little difference in recurrence rate according to estrogen receptor status, he said.
"The take-home message is, I think, the T1a’s have too low of a risk of distant invasive recurrence to justify chemotherapy or trastuzumab," Dr. Fehrenbacher said in an interview. "We need to specifically individualize the risk of the patient based on the size of their primary [tumor], because the T1a’s and T1b’s are quite different in our findings."