Friday, August 15, 2014

Breast Cancer Chemotherapy Varies Widely: Study Raises Questions About Early Treatment Choices

Last month, the Journal of Clinical Oncology reported that six chemotherapy regimens commonly given to patients with early-stage breast cancer vary widely in their side effects. The researchers found that some drug combinations are more likely to lead to hospitalization than others.
The finding, while hardly surprising, points to the value of patients and doctors having fuller discussions about chemotherapy choices. An accompanying editorial emphasizes that because most patients are likely to live for a long time after initial therapy for breast cancer, and options abound, chemotherapy decisions should be more granular than is typical in practice.
The takeaway is that major differences exist among chemotherapy regimens that are routinely given to patients with early-stage breast cancer. Taking “it,” chemotherapy, is not an all-or-none decision.
This matters because over 230,000 people – almost entirely, but not exclusively women – will receive a new breast cancer diagnosis this year in the United States. Most will have early-stage disease. And while many of those individuals will consider if they should have chemotherapy, or not, very few will ask their oncologists details about specific drug combinations.
Their hesitation is understandable. The chemotherapy regimen names sound like gobbledygook, acronyms loaded with A’s for Adriamycin (aka doxorubicin), C’s (cyclophosphamide), T’s (docetaxel, a taxane most often branded as Taxotere) and P’s (paclitaxel, another taxane, aka Taxol). Yes, it gets confusing. The drugs can be given in different combinations, at distinct doses and frequencies, such as every two weeks, or every three weeks. There are many permutations. This is the kind of thing that oncologists study, and patients rarely know much about before beginning treatment.
But maybe they should. Recent articles point to the fact that patients may be legitimately concerned about the costs of various cancer treatment options. Some suggest that doctors should somehow know or find the answers to their reasonable financial questions. But what about the physical, health-related side effects of the drugs?
The new study looked at various combinations of what’s called adjuvant – or extra – therapy for breast cancer after surgery. As reviewed in the paper, multiple randomized controlled studies have established that giving chemotherapy to a newly-diagnosed patient, after surgery for an invasive tumor of at least a certain size, lowers the chances that it will spread or otherwise recur.
The main finding was that for women under age 65 with early-stage breast cancer, the rate of hospitalization for chemotherapy-related problems ranged between 6 and 10 percent. The differences between regimens were statistically significant. In older women the hospitalization rates were significantly higher for all regimens evaluated, ranging between approximately 13 and 24 percent.
As the authors consider, the probability that patients will develop side effects may be predicted, in part, by their age and other health problems, besides which drugs they’re prescribed and the doses given. Taxotere, for instance, has become a more popular drug in recent years and tends to cause neuropathy. Adriamycin, an older drug used for treating many cancer types, may cause heart problems and lower blood counts, sometimes dangerously. Like other chemotherapy drugs in its class, Adriamycin slightly raises the recipient’s chances of developing leukemia later on, especially if it’s given in combination with radiation therapy.
English: Six bottles of different types of can...
Six bottles of different types of cancer drugs (source: Wikipedia, adapted from a National Institutes of Health image)
My intention is not to outline all the possible side effects of these drugs, but to give the reader a sense of how loaded a topic this is. It’s hard for a patient, however well-educated, to know what questions to ask.
To carry out this retrospective analysis, which was admittedly limited in its scope, the investigators culled information for patients with Stage I, II or III breast cancer found between 2003 and 2007. They used two databases: one for those over age 65 (a Medicare-linked registry) and those under 65 years (MarketScan). Based on coding for diagnoses, chemotherapy drug bills and hospitalizations, the researchers determined when patients who received certain drug combinations entered the hospital within six months of treatment.
Hospitalization, per se, is usually a short-term side effect and was the only measured outcome in this study. Neutropenia, meaning a low white blood count, when accompanied by fever is another immediate toxicity of some chemotherapy regimens and is relatively straightforward to assess. Mouth sores and hair loss, and nausea, happen during treatment and then go away. But things like frailty, or depression, or long-term cognitive defects, neuropathy – those can be harder to measure and know.
This paper doesn’t cover newer drugs typically given in Her2 positive cases, sometimes in combination with the older “A” “C” and “T”-like chemotherapies. And it’s worth noting a shift in recent years toward prescribing endocrine treatment, sometimes without chemotherapy, for women with hormonally- sensitive small tumors. The study doesn’t examine toxicities of anti-estrogens, like Tamoxifen, or aromatase inhibitors, of which there are several on the market. But they, too, have significant side effects, some subtle, which warrant detailed evaluation.
Whether a patient gets “AC,” as I did eleven years ago, or “T+AC,” or “dose-dense AC + P” or a newer regimen may seem like a trivial decision to an oncologist who gives these drugs to women with early-stage breast cancer like butter on bread, algorithmically based on his or her community’s local practice. But the differences in outcomes – over the long and short term – are worth examining further.
My conclusion is that this retrospective analysis doesn’t offer enough information, in itself, to guide any woman’s decision about chemotherapy. Or a doctor’s advice. But it suggests that we should collect more nuanced data, over years and decades, about how women fare after treatment for early-stage breast cancer.

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