Study may revise clinical approach to invasive lobular breast carcinoma
- 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.
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.
Contact: Laura Sussman
lsussmanmdanderson
713-792-0655
University of Texas M. D. Anderson Cancer Center