Breast Cancer : Adjuvant Therapy, Drug Therapy

by Food and Drug Administration (FDA)

(Page 2 of 4)

Many factors govern the patient's reaction, she says, and much depends on the individual's psychological defenses and interpretation of treatment outcome. For example, for one woman, treatment with lumpectomy helps minimize her concern about the disease because she is reassured by the less extensive surgery. The continued presence of her breast increases her comfort and reduces her fear. But another woman may react to the preserved breast with a concern over whether or not "they got it all."

Women who have multicentric breast cancer (cancers that develop at several locations within a single breast), or whose tumors are large relative to breast size and therefore would not have a good cosmetic result, are among those who may not be candidates for breast conservation.

No single procedure can be recommended as ideal for all patients. Women and their surgeons must base their decisions on the patient's medical status and her particular concerns. Her choice may be influenced by emotional considerations, finances, access to care, body image, and personal beliefs.

Adjuvant Therapy

Following either mastectomy or lumpectomy with radiation, additional (adjuvant) therapy is given to most women whose cancer has spread to the lymph nodes. This may be chemotherapy or hormone therapy, or both. A current controversy in treatment concerns whether or not to treat node-negative breast cancer patients (patients in whom the disease has not spread to the lymph nodes) with adjuvant therapy. Seven of 10 node-negative women will never have a recurrence of disease. Of the remaining three, standard adjuvant therapy will prevent recurrence in one. Unfortunately, there is no way yet to predict which three will have a recurrence, nor which one of those will be helped by adjuvant treatment. The dilemma, says NCI's Bates, is, "Do we treat 10 to help one, and potentially three if our treatments can improve?"

The NIH consensus panel concluded that, "The decision to use adjuvant treatment [in node-negative patients] should follow a thorough discussion with the patient regarding the approximate risk of relapse without adjuvant therapy, toxicities of therapy, and its impact on quality of life." They further agreed that, except for patients in clinical trials, "it is reasonable not to employ adjuvant therapy in patients with tumors 1 centimeter or smaller because their chance of recurrence is less than 10 percent in 10 years." For patients with larger tumors, other predictors of recurrence should be considered.

Drug Therapy

Many drugs have been tried alone and in combination to find the best regimen to treat breast cancer. Cancer drugs can have serious side effects. They are designed to kill cancer cells, but they also affect other rapidly growing cells, such as blood-forming cells and those that line the digestive tract. As a result, they may lower resistance to infection, sap energy, and cause bruising or bleeding, nausea, vomiting, mouth sores, loss of appetite, hair loss, and other side effects. Pre-menopausal women may also experience hot flashes, vaginal dryness, painful intercourse, and irregular menstrual periods.

For 42-year-old Ellen Weinberg of Chevy Chase, Md., the choice of treatment came with the chemotherapy, not surgery. (Because her cancer was multicentric, Weinberg had a total mastectomy.) She saw two oncologists about adjuvant therapy and got two different opinions.

"That's really where I was hoping there would be no discrepancy — that both would say the same thing. But of course they didn't," she says. One recommended CMF — a combination of cyclophosphamide (Cytoxan), methotrexate, and 5-fluorouracil. The second oncologist told her about CMF and another regimen, CAF, which uses doxorubicin hydrochloride (Adriamycin) instead of methotrexate. "He said that CMF would be fine for me and that CAF was a more aggressive treatment — that I would probably have more severe side effects with it, but he described adriamycin as having a very good track record."

Weinberg chose the CAF. "I knew I was buying myself a whole lot of trouble short-term and I didn't know if the result was going to be any different long-term. And everyone said the prognosis was real good anyway. It was a sort of agony, but I came to that decision and I felt very comfortable with it."

Side effects of chemotherapy vary with each patient, according to the treatment given and the individual's reaction. Weinberg, who has had three of six treatments so far, says that for her, it is like being very sick with the flu. "You feel hot, cold, very lethargic, you get strange tingles and pains. Some people get achy. I feel toxic. I can't describe it any other way." She also had severe vomiting after the first treatment, but less so with the second, when she was given Marinol (oral marijuana derivative) to help reduce the vomiting. With the third treatment, Weinberg was given ondansetron hydrochloride (Zofran), which FDA had just approved (in March 1991) to combat nausea and vomiting associated with cancer chemotherapy. With Zofran, she didn't vomit at all, but the other side effects remained.

Hormone therapy, usually in the form of a drug called tamoxifen (Nolvadex), is most often given to women whose cancer cells are estrogen-receptor positive. Tamoxifen blocks estrogen from binding to the cell's receptors for that hormone, thus keeping the cells from getting the hormones they need to grow. Originally approved by FDA in 1977 for patients with advanced breast cancer and subsequently for patients with less severe disease, tamoxifen was approved for use in node-negative patients in June 1990. Hormone therapy can also produce a number of side effects, but they are usually not severe. They may include symptoms of menopause, such as hot flashes, missed periods, and vaginal dryness.

Tamoxifen is also being studied in England as a preventive agent for breast cancer, and a similar study is planned in the United States. NCI is funding a study by the National Surgical Adjuvant Breast Project, which will be designed to test the effectiveness of this drug in preventing a first occurrence of breast cancer. The study will eventually include about 16,000 women at high risk for the disease.

Treating Advanced Disease

Breast cancer that has advanced to Stage III or IV (see accompanying article, "Determining Therapy") requires chemotherapy or hormone therapy, or both, to treat its spread. Treatment may also include surgery or radiation therapy, or both, to control the breast tumor. Hormone therapy may be accomplished with drugs such as tamoxifen or, in pre-menopausal women, by removing the hormone-producing ovaries. Women whose cancer has spread beyond the breast to other parts of the body usually have less extensive breast surgery, but receive hormonal therapy or more aggressive chemotherapy directed to treating both local and metastatic disease. If necessary, radiation may be used for local control.

Most tumors eventually develop drug resistance. New treatments under study for patients with advanced breast cancer involve removing some of the patient's bone marrow and administering high-dose chemotherapy to overcome drug resistance. This is followed by reinfusing the bone marrow to prevent life-threatening drug toxicity. This therapy is also being tried in patients at high risk of disease recurrence.

About the Author

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