Hormone Responsive Breast Cancer in Younger Women May Need More than Chemotherapy

LEIDEN, The Netherlands, Oct. 11 -- Young women with estrogen receptor-positive breast cancer may not get as much benefit from chemotherapy as those with estrogen receptor-negative disease, researchers said.

Women with estrogen receptor-positive tumors survived longer than those with estrogen receptor-negative tumors overall (P=0.02), but the survival advantage disappeared for those who received chemotherapy as their only adjuvant treatment (P=0.63), according to a pooled retrospective analysis of four trials reported online in the journal Breast Cancer Research.

"These results confirm that chemotherapy alone cannot be considered optimal adjuvant systemic treatment in breast cancer patients 40 years old or younger with hormone receptor-positive tumors," wrote Cornelis van de Velde, M.D., Ph.D., of Leiden University Medical Center here, and colleagues.

Because the findings support previous meta-analyses, "the next obvious statement would be that these patients with estrogen receptor-positive tumors really should get hormonal therapy," commented Ellen Chuang, M.D., of Cornell University Medical Center in New York, who was not involved in the study.

Whether chemotherapy can be avoided entirely for these women is still controversial, with most oncologists in the United States are reluctant to treat young women with hormonal therapy alone, she said.

But the traditional use of chemotherapy, regardless of tumor biology, for women at high lifetime risk of recurrence may be giving way to studies like Dr. van de Velde's and a similar study looking at human epidermal growth factor receptor type 2 (HER2) status reported in the Oct. 11 New England Journal of Medicine. (See: HER2 Status Affects Chemotherapy Benefit for Node Positive Breast Cancer)

"I do believe in the next two or three years we are going to be able to combine a number of factors and identify those patients who are so unlikely to benefit from chemotherapy that they shouldn't take it," commented Daniel F. Hayes, M.D., of the University of Michigan in Ann Arbor, lead investigator in the HER2 study.

Dr. Chuang agreed, "That is really where this field is going."

Dr. van de Velde and colleagues analyzed data from four European Organization for Research and Treatment of Cancer (EORTC) trials. These trials included 934 early stage breast cancer patients 40 or younger at the time of diagnosis, of whom 480 had tumor samples available for immunohistochemistry analysis.

Although each trial had a different focus, adjuvant chemotherapy was either CMF (cyclophosphamide, methotrexate, and fluorouracil [Adrucil]) or an anthracycline-based regimen (fluorouracil and cyclophosphamide with doxorubicin [Adriamycin] or epirubicin [Ellence]).

Among the 279 women who received adjuvant chemotherapy, 85% were lymph node-positive. Nearly all of the 201 who did not receive chemotherapy were node-negative (94%).

Estrogen receptor status was positive for 288 women. Progesterone status was positive for 223. Less than 5% of the women received adjuvant hormonal therapy, though, because it was not yet recommended at the time the trials were done.

After a median of 7.3 years of follow-up, 22% of the participants had died and 32% had developed a distant recurrence or died.

In the total cohort, estrogen receptor-positive tumors were associated with 37% better overall survival (hazard ratio 0.63, P=0.02) but not distant metastasis-free survival (HR 0.90, P=0.51) compared with estrogen receptor-negative cancer.

Likewise, progesterone receptor positivity was associated with better overall survival (HR 0.59, P=0.01) but not distant metastasis-free survival (HR 0.78, P=0.14).

Even after controlling for nodal status, tumor size, and chemotherapy in multivariate analysis, both hormone receptors were significant factors in overall survival.

When stratified by chemotherapy use, the findings included:

• Overall survival was better for estrogen receptor-positive than negative tumor status without chemotherapy (HR 0.41, P