Long-Term Chemo Side Effects in Breast Cancer

Most breast cancer patients are treated with some form of chemotherapy, and because patients are now surviving longer, the long-term effects of chemotherapy have become a major issue. At the 30th Annual Miami Breast Cancer Conference, Hyman Muss, MD, professor of medicine at the UNC Lineberger Comprehensive Cancer Center in North Carolina, gave a presentation today on both the long-term side effects of treatment with chemotherapy and ways to deal with these issues.

“When you are discussing long-term side effects of chemotherapy, you are talking about adjuvant chemotherapy,” said Muss. “Women with advanced breast cancer who receive chemotherapy-it's essentially, and unfortunately, palliative care,” Muss added. The current 5-year survival rate for women with stage II breast cancer ranges from 74% to 81%, but only 15% for those with stage IV disease.

Current adjuvant breast cancer chemotherapy regimens can be grouped into categories-more aggressive anthracycline- and taxane-based therapies, and less aggressive regimens such as docetaxel and carboplatin. “Docetaxel and carboplatin have been found to be superior to the traditional chemotherapy combination of doxorubicin and cyclophosphamide,” said Muss. While anthracycline -based regimens have cardiac toxicities and potentially a higher risk of secondary leukemia development, docetaxel and carboplatin do not have an appreciable risk of either. For HER2-positive patients, chemotherapy is combined with trastuzumab, an anti-HER2 antibody. A study has demonstrated that the combination of trastuzumab with docetaxel and carboplatin in HER2-positive patients is associated with lower cardiac toxicity compared to anthracycline-based regimens. The combination of trastuzumab with anthracyclines is not recommended as this combination can result in severe cardiac dysfunction.

The type of adjuvant regimen a patient receives depends on risk of recurrence as well as a physician’s treatment philosophy, according to Muss. Higher risk patients include triple-negative breast cancer patients as well as those with multiple positive lymph nodes.

The more aggressive regimens require growth factors and come with much short-term toxicity. “But, they have made a major impact in improving survival for patients with high-risk breast cancer,” said Muss.

Despite the short-term regimen schedule-anywhere between 12 and 18 weeks-longer-term issues and adverse events are common. For younger breast cancer patients fertility is an important long-term issue. “That is always something that needs to be discussed upfront,” Muss noted. While younger women in their 30s can recover their menstrual cycle, fertility is still a major issue after chemotherapy. Younger patients are referred to fertility specialists for in vitro fertilization and oocyte-freezing, among other options.

Another common long-term toxicity for patients is fatigue, for which there is no magic pill or simple solution. One potential remedy is exercise. Studies have shown that exercise can reduce fatigue in cancer patients. “Perhaps counter-intuitively, but we always tell patients to exercise to boost their energy levels,” said Muss. Muss cautions that fatigue could be a signal for an underlying problem such as anemia, hyperthyroidism, depression, or a secondary chemotherapy-related cancer all of which should be explored and not missed. In general, studies have shown that behavior modifications, yoga or acupuncture could be helpful for a subset of patients. “Anything that is good for a patient’s overall health such as exercise is certainly worth encouraging,” said Muss.

Taxane-based chemotherapy tends to lead to neuropathy which may be a major problem. According to Muss, neuropathy is slow to resolve for patients who have received chemotherapy or may not resolve at all. In older patients, neuropathy can lead to poor balance and could cause falling and other complications. “We have not found any way to prevent this toxicity,” said Muss. A recent study presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in 2012 showed that about one-half of cancer patients with chemotherapy-induced neuropathy had symptom relief from duloxetine (Cymbalta), an antidepressant drug. “Duloxetine is certainly worthy of consideration, but the drug does come with a lot of its own toxicity which needs to be taken into account,” said Muss.

Another long-term adverse events is cardiac damage, especially with doxorubicin or other anthracyclines. But, Muss noted that because lower anthracycline doses are now used and because anthracycline is now less frequently used to treat breast cancer, the frequency of cardiac issues has decreased. Secondary cancers are also an issue. As many as 20% of breast cancer patients are diagnosed with a secondary cancer, therefore screening is important.

Muss stressed the importance of maintaining a healthy lifestyle for cancer patients, to minimize risk of other types of cancers and for the general wellness of the patient. “Patients should keep up a healthy body mass index, eat a low-fat diet, and exercise,” said Muss.

In general, patients taking adjuvant chemotherapy will recover in a few months and have a relatively good quality of life, according to Muss.