What are the short term side effects from chemotherapy? Clearly alopecia in most of the regimens used. Weight gain is very common. This always comes as a shock to patients. Fatigue is the overwhelming most common and problematic problem from adjuvant chemotherapy. Febrile neutropenia is quite rare. Neutropenia is quite common. It usually occurs with every course but febrile neutropenia is quite rare and hemorrhagic complications are even more rare.
Of more concern are the long term side effects from adjuvant chemotherapy particularly if you’re treating young women. It can cause premature menopause and then these women have usually not been thought to be eligible for hormone replacement therapy and are at risk for cardiovascular disease and osteoporosis.
If you look at women treated with adjuvant chemotherapy and compare them to women who have not had breast cancer and not been treated, their incidence of leukemia is actually fairly comparable. Now, there are some investigational arms who escalated doses of cytoxan where leukemia incidence appeared to be increased. But in the general adjuvant therapy we’ve given over the past few years, leukemia doesn’t appear to be increased, nor does cardiomyopathy.
Tamoxifen needs to be used at least more than two years and probably for five years and probably not for more than five years. At more than five years, there may actually be an ability for tumor cells to learn to use tamoxifen to grow and you have increased relapse of breast cancer with more than five years of tamoxifen. You also have an increased risk for other tumors, particularly uterine cancer. It clearly benefits people who are postmenopausal more than premenopausal and usually only those patients who are ER/PR positive will benefit the most. PR positive ER negative benefit also.
Tamoxifen, and you probably have heard so much about tamoxifen in the last few weeks you can’t stand it, probably benefits bone density and blood lipids. In the trial for prevention of breast cancer in normal women, they couldn’t really show that but with only four years followup I don’t think that’s so surprising and I think with longer followup they may be able to demonstrate that. But clearly in breast cancer patients we’ve known for a long time it reduces the risk of contralateral breast cancers by 50%. I think it reduces the risk of new breast cancers in the lumpectomy radiated breast and now we know that in women at risk for breast cancer who have not had breast cancer, tamoxifen reduces the risk of getting breast cancer.
What is the role of adjuvant radiation? I think the thinking about this has changed quite a bit in the past few months. I used to say that local radiation therapy only prevented relapse in the local area and didn’t do anything much for overall survival. There’s two very impressive articles in the New England Journal in October of last year and it showed that patients with any positive nodes receiving radiation therapy had a better survival when that was combined with chemotherapy versus chemotherapy alone. Most of the chemotherapy was with cytoxan methotrexate 5FU. Even in patients who had few nodes, one to three positive nodes, these are the patients who got radiation and chemotherapy versus chemotherapy alone, they seem to have a survival benefit.
In the past I had only applied radiation to patients with four or more positive nodes or large tumors or invasion of the chest wall or something like that. I am now radiating everyone with positive nodes. That may not be standard in all places.
What is the followup for patients who have had breast cancer and then adjuvant therapy or even just breast cancer? See a physician with a good history and physical every four months for the first two years and then every six months to complete five years and then yearly has been my practice and I think is fairly standard. I do a CBC and chemistry profile. You could argue that a CBC is not really necessary. The most important thing is clearly the physician breast exam, the yearly mammograms and other health care maintenance should be followed such as yearly pelvic exam, screening for blood in the stools and sigmoidoscopy after age 50.
Diagnosis and Treatment of Breast Cancer