Physicians Put on the Gloves to Debate Best Treatments in Breast Cancer

Patrick I. Borgen, MD

The tradition of lively Medical Crossfire debates continued at the 33rd Annual Miami Breast Cancer Conference this year, with three bouts involving four physicians.

Should platinum-based or other additional systemic agents be used in high-risk triple-negative breast cancer (TNBC)?

Matthew Ellis, MD, PhD

Debu Tripathy, MD

Here are the questions and a summary of what the combatants had to say.Yes. The question of how to augment standard chemotherapy to reduce the risk of recurrence in very high-risk cases—especially TNBC—remains a challenging one: some oncologists already are using platinum agents in this way. Promising findings of studies were presented at ASCO and SABCS (eg, CALGB 4063, GeparSixto), showing the number of patients achieving a complete pathologic response is higher with neoadjuvant carboplatin in TNBC. Researchers are awaiting more data from two large trials to confirm a survival benefit.No. It is too early to routinely recommend additional chemotherapy in patients with high-risk TNBC. Studies assessing the addition of platinum agents in the neoadjuvant setting do show higher complete pathological response, but the more relevant benefit of adjuvant chemotherapy is long-term impact on recurrence and mortality.

This has not yet been shown when using a standard chemotherapy backbone. One recently presented but not yet published trial (CREATE-X) does deserve some attention. It involves the use of capecitabine in patients who have residual disease after neoadjuvant chemotherapy. This trial enrolled both hormone receptor—positive and –negative, HER2-negative cancers and showed improved survival over the control arm with 6-8 cycles of capecitabine postoperatively.

Is it time we stopped offering mastectomy to patients with breast cancer?

J. Michael Dixon, MD

Once published and subjected to commentary, this could either with confirmation or on its own represent a potential treatment, but only after neoadjuvant therapy—as residual disease could identify those most likely to benefit.Yes. At one time, you used to say that breast conserving surgery was at least equivalent to mastectomy. It’s now looking better for some patients than mastectomy, and there are reasons for that because mastectomy is not the best operation.

Patrick I. Borgen, MD

Should all stage II patients begin their treatment with systemic therapy prior to surgical intervention?

Dixon

It leaves breast tissue behind. With mastectomy alone, if you’ve got a cancer with lymphatic vascular invasion, you’re relying on systemic therapy to get rid of any disease in lymphatics, and you leave lymphatics underneath the skin which are untreated. With radiotherapy, you treat a much bigger volume of tissue properly. So, there are many reasons why radiotherapy after breast conserving surgery may give you a better survival and better outcome than mastectomy. And yet there’s still this big rise in mastectomy rates. I think you’ve got to give patients the facts, and the fact is at the moment for some of these patients, the balance of evidence is actually swinging toward breast conserving surgery. And you should only give patients a choice where there’s very equal outcomes. In our unit [in the United Kingdom], we don’t give patients a choice. If you’re suitable for breast conserving surgery, then we’re going to do breast conserving surgery. It’s most cost effective; the patients are out of the hospital quicker; there are fewer complications. Your survivals are at least as good and probably better. So, for me, it’s time to stop giving patients a choice.No. My record as a passionate proponent of breast conserving approaches to breast cancer treatment has been well established and documented over a 25-year career. It is always my preferred approach where appropriate, but experience has taught me that it is not the right option for all patients. Many factors go into the choice between conservation and mastectomy and those need to be part of a global and comprehensive risk/ benefit discussion. The argument that there may be a survival advantage associated with breast conservation over mastectomy is confounded by a number of factors, including the application of external beam radiation therapy. Even if the modest survival benefit proves durable it should become part of the discussion. Not giving patients all the options is simply not an option.Yes. The best way to know whether you’re going to survive breast cancer is to know whether you’re going to respond to your drug therapy. And so, if you look at all the neoadjuvant chemo trials, the biggest and the best prognostic indicator is whether your cancer is responsive and is killed completely by the treatment. The trouble at the moment is, the way we treat patients is we take the cancer out and then we give them the drug therapy afterward, and we have absolutely no idea whether that therapy is effective. We only find out that we’re wrong when the cancer recurs, and that’s too late. There are now ways to identify patients who are going to respond and who aren’t going to respond.

Borgen

If you treat a patient with a couple weeks of hormone treatment, then look at their cancer after a couple of weeks, you can tell whether that patient is going to benefit long term from that therapy with a much, much, much greater certainty than you can by any of the current prognostic tools based on the cancer at diagnosis. We need to challenge the cancer with some kind of drugs and work out whether they’re going to respond. For those that do respond you can treat them with that drug, but for those that don’t, we need new trials and better treatments. So, the future has to be everybody getting some drug therapy at the start.No. There is tremendous value in neoadjuvant therapy approaches to many patients with breast cancer. The advantages are many: beginning systemic therapy at the earliest possible moment, having an in vivo response barometer, a chance to change therapies that are less effective than planned, and a chance to minimize tissue loss and improve surgical margin status. These are inarguable benefits to this approach, but mandating systemic therapy a priori in all patients is yet another form of over-legislation that detracts from the subtleties and vagaries of the doctor-patient relationship. Neoadjuvant therapy is not right for all patients and our goal should be to precisely match our treatment recommendations for a given breast cancer to the individual patient and her values, goals, priorities, and sensibilities. Medicine is still an art as well as a science and, even in our increasingly complex field, there is plenty of room for old-fashioned judgment.