Adjuvant Therapy Even for Small Tumors

An important new study published in the Journal of the National Cancer Institute has determined that even women with very small tumors—1 cm or less—can benefit from adjuvant (additional) chemotherapy and/or tamoxifen therapy after their tumors are removed.

This so-called "adjuvant therapy"—treatment that is given in addition to the primary treatment (in this case lumpectomy)—greatly minimizes the risk of cancer recurrence, according to Dr. Bernard Fisher and colleagues of the Pittsburgh-based National Surgical Adjuvant Breast and Bowel Project.

Fisher’s team evaluated the impact of giving this adjuvant therapy to 1,259 women who had lumpectomies for tumors that were 1 cm or less in size and had no disease spread to their nearby lymph nodes. Of this group, 235 women had tumors that were not sensitive to estrogen (estrogen receptor-negative or ER-negative), and 1,024 had estrogen-receptor positive (ER-positive) tumors.

For the 235 women whose cancer was not stimulated by estrogen (ER-negative), adjuvant chemotherapy after their lumpectomy increased their eight-year relapse-free survival to 90 percent, compared to 81 percent if they had surgery alone.

For those women whose tumors were stimulated by estrogen (ER-positive), 93 percent survived relapse-free for eight years when chemotherapy was given after their surgery, compared to 86 percent if only surgery was offered. When both tamoxifen and chemotherapy were given, relapse-free survival rose to 95 percent.

The researchers noted that the standard thinking of "the smaller the tumor, the lower the risk of recurrence" is not adequate anymore. "The prognosis for women with tumors of 1 cm or less, while better than that of women with larger tumors, is not good enough to preclude them as candidates for systemic therapy," the authors concluded.

Nonetheless, in an accompanying editorial, Drs. Marc Lippman and Daniel Hayes of the Georgetown University Medical Center in Washington expressed caution about undertaking such additional therapy for much smaller tumors (9 mm or less) in the absence of definitive clinical trials.

NIH Recommendations

The above study comes on the heels of similar findings by a panel of breast cancer experts convened by the National Institutes of Health (NIH). Their objective was to find some type of consensus on the best adjuvant therapies for treating breast cancer at its various stages.

Dr. Patricia Eifel of the M.D. Anderson Cancer Center, the chairwoman of the NIH panel, reported on three of their major recommendations regarding adjuvant therapies for breast cancer:

• Most women with localized breast cancer should receive combination chemotherapy, which uses a number of different chemotherapies instead of just one drug. They should consider taking this combination treatment for three to six months after surgery to make sure any remaining cancer cells in their bodies are killed.
• The panel recommended that women whose breast cancer may have been stimulated by estrogen (ER-positive) should undergo adjuvant hormonal therapy for five years after surgery, regardless of their age. This typically involves taking the drug tamoxifen. However, the benefits of taking hormonal treatment longer than five years has not been established, they warned.
• The panel suggested that adjuvant radiation therapy—in addition to combination chemotherapy and/or hormonal therapy—could benefit women at high risk of recurrence. This includes women with evidence of cancer in at least four lymph nodes or with an advanced primary tumor, especially if a mastectomy was required. They cautioned, however, that the benefits of radiation for women with fewer than four positive lymph nodes are unknown.

Further Evidence

A month prior to the NIH consensus conference, similar findings were presented at the 2^nd European Breast Cancer Conference in Brussels, Belgium. These showed that adjuvant treatments for breast cancer, including radiotherapy, chemotherapy, and in particular the hormone treatment tamoxifen, prevent later recurrences of the disease.

Oxford’s Sir Richard Peto presented the composite results of 300 randomized trials that included approximately 200,000 patients. "This is the first time we’ve had good evidence on the effects of treatment on 15-year survival," Peto said.

Peto noted that the use of such adjuvant therapies reduces relapses because they also directly target dormant disease. Therefore, he said, you not only get a benefit while you are currently receiving the adjuvant therapy, you also get an additional benefit accumulating in the 5 or 10 years after you’ve stopped. This is because of its impact on killing undetected microscopic cancer cells.

Peto also argued for the use of combination therapies, particularly hormonal therapy (tamoxifen) and chemotherapy. "If a woman has estrogen receptor-positive disease, then hormonal treatment works well," he said. "But so does chemotherapy. These aren’t mutually exclusive. It’s not a question of which is better ... one shouldn’t let the use of one therapy preclude the use of the other."

SOURCES:

Journal of the National Cancer Institute, January 17, 2001; 93:80-83, 112-120
NIH Consensus Development Conference on Adjuvant Therapy for Breast Cancer, National Institutes of Health, November 1-3, 2000, Bethesda, Maryland
"Adjuvant Therapy for Breast Cancer," NIH Consensus Development Conference Statement #114, (http://odp.od.nih.gov/consensus/cons/114/114_statement.htm)
2^nd European Breast Cancer Conference, October 2, 2000, Brussels, Belgium

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