Poor response to chemotherapy does not mean poor outcome for patients with rare breast cancer

December 29, 2004

HOUSTON - Women with a rare type of advanced breast cancer who do not benefit from primary (pre-surgical) chemotherapy still have been found to do better in the long run than patients with a more common advanced breast cancer who do respond to chemotherapy.

Researchers at The University of Texas M. D. Anderson Cancer Center came to the surprising conclusion after discovering that chemotherapy response did not seem to impact survival in women with invasive lobular carcinoma the same way that it does for patients with invasive ductal carcinoma.

Results of the study show women with this lobular form of cancer may not need chemotherapy before surgery, the researchers report in January issue of the Journal of Clinical Oncology.

"This is a striking finding, the first to find that in a type of breast cancer, response to chemotherapy seems to have little to do with long-term treatment success," says the study's lead author, Massimo Cristofanilli, M.D., associate professor in the Department of Breast Medical Oncology at M. D. Anderson.

The results came from a retrospective study of six clinical trials that treated 1,034 women with stage II and III invasive breast cancer (lobular or ductal) with primary chemotherapy in order to shrink their tumors before surgery.

"We always have thought that a poor response to chemotherapy always indicated a worse prognosis, but that is not true for every woman with breast cancer because this disease is quite heterogeneous," Cristofanilli says. "In fact, this study suggests women with invasive lobular carcinoma have a different kind of disease, and that they may benefit from a treatment that is more adequately tailored to the biology of their cancer.

"Before this study, I don't think anyone realized the disease should be treated differently," Cristofanilli continues. "Now we need to think about revising our clinical approach and, more importantly, the way we communicate prognosis to women with lobular cancer that have shown poor response to chemotherapy."

Such a change in the clinical approach may involve use of hormonal therapies, Cristofanilli says, because the team previously found that whether or not women with invasive lobular carcinoma achieved a complete response, they tended to have a better prognosis even compared with invasive ductal carcinomas that are hormone receptor positive (typically a better prognosis group).

Use of hormonal therapies such as aromatase inhibitors "may represent an interesting approach to treating invasive lobular carcinoma," and that use of systemic chemotherapy might be limited to women with inoperable invasive lobular carcinoma tumors, he says.

"In the end, our study indicates that primary chemotherapy, with its toxic effects, may not be the best standard of care for women with invasive lobular carcinoma," Cristofanilli says. "Additional investigation, including genomic and proteomic studies, are warranted to help clarify the unique biological features of this disease."

Invasive lobular carcinoma is the second most common type of invasive breast cancer after invasive ductal carcinoma, according to the researchers, and accounts for five to 15 percent of all breast cancer cases. The cancer develops in the lobules of the breast, the glands that make breast milk. Ductal carcinoma, on the other hand, develops in the milk duct vessels that extend from the lobules to the nipple.

Overall, use of neoadjuvant chemotherapy has proven successful in treatment of locally advanced breast cancer (that which has spread out into the breast or to adjacent lymph nodes) and is now standard treatment for the disease. Neoadjuvant chemotherapy provides an early mean to test the whether a patient will respond to the treatment, which could then reduce the size of breast tumors so that breast conservation surgery might be an option.

M. D. Anderson pioneered use of the neoadjuvant chemotherapy for breast cancer through a series of clinical trials conducted at the institution between 1985 and 2002. But patients were not divided by tumor histology within these studies because too few women had invasive lobular carcinoma. Now, by combining these trials together, Cristofanilli and his research team had enough patients (122 with invasive lobular carcinoma and 912 with invasive ductal carcinoma) to better understand possible effects of treatments on response and outcome.

They evaluated the impact of "histological" type of cancer - determined from tumor biopsies - on the likelihood that patients would achieve a "pathological complete response," on evidence of cancer remaining in the breast or lymph nodes, and on long-term outcome.

What they found was contrary to what they had anticipated. Women with invasive lobular carcinoma had a poorer response to primary chemotherapy yet better overall survival. Specifically, only 3 percent of lobular carcinoma patients had a pathological complete response, compared to 15 percent of ductal carcinoma patients; 41 percent of women with lobular cancers had residual lymph node disease compared to 26 percent of women with ductal disease.

Yet, five years after treatment, breast cancer had not come back in 80 percent of women with lobular carcinoma, compared with 66 percent of ductal carcinoma patients. And five-year survival in women with invasive lobular carcinoma was significantly higher - 91 percent - compared with 72 percent in women with invasive ductal carcinoma.
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The study was funded by the Nellie B. Connally Breast Cancer Research Fund and the Susan G. Komen Fellowship Fund. Co-authors include principal investigator Gabriel Hortobagyi, M.D., chairman of the Department of Breast Medical Oncology; Ana Gonzalez-Angulo, M.D.; Nour Sneige, M.D.; Shu-Wan Kau, Kristine Broglio, Richard Theriault, D.O.; Vicente Valero, M.D.; Aman Buzdar, M.D.; Henry Kuerer, M.D., Ph.D.; and Thomas Buchholz, M.D.

University of Texas M. D. Anderson Cancer Center

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