Preserving Flexibility in Chemo Decisions in Breast Cancer

Andrew Seidman, MD

The accumulation of evidence supporting a regimen of anthracycline and taxanes for breast cancer has led some oncologists to argue for the establishment of a standard treatment plan that deemphasizes or eliminates alternative options.

“The idea is that if you’re going to give chemotherapy, give the very best chemotherapy,” said Andrew Seidman, MD, a professor of medicine at the Weill Cornell Cancer Center and an attending physician at Memorial Sloan Kettering Cancer Center.

Seidman, however, disagrees with that position. He will lay out his argument against what he calls a “one-size-fits-all” regimen for early stage breast cancer during this afternoon’s Medical Track program at the 33rd Annual Miami Breast Cancer Conference®.

As an example of the call for use of a single best regimen, he cites a 2012 editorial in the Journal of the National Comprehensive Cancer Network by Harold Burstein, MD, PhD, an associate professor of medicine at Harvard Medical School and medical oncologist at Dana-Farber Cancer Institute and Brigham and Women’s Hospital.¹

Burstein critiques permissiveness in treatment guidelines, writing, “inclusiveness comes at a price. It enables variation in practice that may be confusing or unnecessary, potentially raising questions of safety and efficacy for treatment delivery. And it allows guideline panels to skirt the tough questions about which regimens they would ‘really’ recommend or which regimens provide the most value based on activity, toxicity, and cost.”

However, Seidman argues that for early stage breast cancer, the proportional benefit of chemotherapy in reducing the risk of distant metastasis and death for a particular patient, and the comparative toxicity and harm, must be taken into account in selecting a regimen. He pointed to the difference in benefit for a woman with a 6% chance of distant metastasis and a woman with a 60% chance. If a chemotherapy regimen reduces the risk of recurrence and death by one-third, for example, the first woman will have an absolute gain of only 2%, compared with the 20% benefit for the second woman, he said.

“Few would argue with the notion that anthracycline and taxane-containing chemotherapy regimens are the most active agents in breast cancer,” he said. “But I’ll make the argument that based on the patient’s risk, based on tumor biology, also based even on the patient’s comorbidities, other medical conditions, and—to a certain extent—patient preference, that we should be able to be more nuanced in making decisions.”

Seidman said that while dose-dense doxorubicin and cyclophosphamide followed by paclitaxel is considered a preferred regimen, it might not be the best choice, for example, for a 60-year-old woman with 1.5-cm lymph node—negative breast cancer that is hormone receptor–positive and HER2-negative, and who has a high Oncotype DX recurrence score of 34.

“For me, that woman warrants chemotherapy, but for reasons that I’ll cite in my lecture, I’ll make the argument that sometimes less is more, that there are maybe less effective chemotherapy regimens that would be more appropriately suited to this patient than the woman who has a triple negative breast cancer that involves four lymph nodes, for example,” he said.

The newest, most effective generation of chemotherapy may make sense for a patient who could see a large benefit, Seidman said. Suppose the newest regimen increases the proportional benefit from one-third to one-half; the woman with a 60% risk of metastasis would see her benefit increase from 20% to 30%, he said.

“For that additional 10% chance of being free of recurrent metastatic breast cancer, that patient probably should be strongly advised to accept a chemotherapy regimen that increases her risk of nausea and vomiting, that will guarantee that she has reversible but complete hair loss, that has a greater chance of causing peripheral neuropathy, increases the risk of cardiomyopathy in a small percent, and increases the risk of infection,” he said. However, the woman with a 6% risk of metastasis would see only a 1% increase in benefit from that chemotherapy. For such patients, less-toxic treatments, such as the older CMF (cyclophosphamide, methotrexate, fluorouracil) regimen may be appropriate, Seidman argued.

“The difference in the effectiveness of these regimens will translate into a modest absolute benefit, but not so necessarily modest difference in patient experience and toxicity,” he said.

In particular, the differential benefit of the drugs is less important for patients who benefit from antiestrogen drugs, such as tamoxifen or aromatase inhibitors, and for patients with HER2-positive breast cancer whose risk is reduced by using a drug like trastuzumab (Herceptin), he said.

“For me, there is room for nuance,” Seidman said. “It’s nice and easy and convenient to only think of one chemotherapy regimen, but I think an artful medical oncologist can apply the data uniquely to individual patients.”

In addition to Burstein’s editorial, Seidman also referenced an expert panel’s review of early breast cancer therapies at last year’s St. Gallen International Breast Cancer Conference. That panel laid out a set of recommendations while saying that the choice of an adjuvant chemotherapy regimen should reflect the patient’s level of risk. It noted that for “Luminal A—like” tumors there was little advantage to using anthracycline and taxanes compared with older regimens such as cyclophosphamide, methotrexate and fluorouracil (CMF) or doxorubicin and cyclophosphamide (AC).²

References

1. Burstein HJ. Simplifying guidelines: we need only one adjuvant chemotherapy regimen for breast cancer. J Natl Compr Canc Netw 2012;10(7):797-798.
2. Coates AS, Winer EP, Goldhirsch A, et al.; Panel Members. Tailoring therapies-improving the management of early breast cancer: St. Gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol.