When first diagnosed with cancer, it can feel like the surest, fastest way to get rid of it is to cut it out. So many newly diagnosed breast cancer patients are surprised to learn that surgery isn’t the first step in treatment for many people and that it plays a smaller role in survival than many expect. Well-known surgeon Dr. Susan Love has commented for several years when attending SABCS that surgery has less and less to offer and the real improvements are happening in radiation and systemic therapies.
In fact, for many people, surgery shouldn’t be the first step. I spoke with one doctor who said she considers it malpractice to do surgery before treating patients with HER2+ breast cancers with systemic therapy. This is because seeing how triple negative and HER2+ breast cancers respond to treatment before surgery (what’s known as neoadjuvant therapy) predicts how likely the cancer is to recur. This information can guide treatment for better outcomes. Providing additional treatment after surgery, if there is residual disease after neoadjuvant treatment, can cut the risk of recurrence in half. Originally used to down-stage large tumors before surgery, neoadjuvant treatment is now used to assess tumor response to treatment in real time, and to determine the need for additional therapy after surgery.
In the best case scenario, a breast cancer will actually disappear when treated with systemic therapy before surgery. Which leads many patients to ask: “Why do I need surgery if there is no cancer left?” Several studies (GS5-04, GS5-05, GS5-06) looked at whether some patients can avoid surgery altogether—the ultimate breast conserving treatment—using experimental methods to try to reliably predict who can safely omit surgery with no signs of cancer after neoadjuvant chemotherapy.
Only one (GS5-04) of the three studies looking at this question concluded that they could “reliably predict residual cancer using a standardized protocol using image-guided breast biopsy after neoadjuvant chemotherapy, and safely omit surgery in exceptional responders.” But the accuracy was not 100%. Even a small 4.2% false negative for HER2+ and triple negative sub groups forces the question of whether any false negatives more than 0% are acceptable. For high-morbidity surgeries of delicate tissue where patients’ quality of life is significantly impacted, the threshold for missed cancer from false negatives is different than for lumpectomies with relatively manageable morbidity for most people.
Dr. Kalliopi Siziopikou, a pathologist who offered commentary on the topic, explained that there are two ways that residual tumor persists after neoadjuvant therapy. The way that most people imagine that tumors shrink in response to systemic treatment is actually uncommon, which is concentric shrinkage, where a large tumor will melt like a snowball to a smaller tumor. When this happens, sophisticated imaging techniques and core biopsies can identify residual tumors. But it’s much more common for tumors to persist as tiny scattered foci of single cell tumors in a background of chronic inflammation. This is more like hitting a needle in a haystack and is the reason many core biopsies have low accuracy.
The risk of underestimating residual disease leads to the omission of additional adjuvant treatments that may benefit patients. For now, detailed pathological evaluation of tumor response to neoadjuvant chemo in surgical specimens remains the standard.
Despite the eagerness to find new genomic tests to predict risk, often clinical assessment performs as well or better as expensive genomic tools at predicting risk. I appreciated Dr. Enrique Soto’s comment on Twitter (@EnriqueSoto8): “This is upside down. Clinical factors, easy and cheap to obtain, are used to make sense of an expensive genomic test.” He linked to a paper by Dr. Vinay Prasad published this month in the Journal of the Comprehensive Cancer Network (JNCCN), “Clinical Risk During the Evaluation of Genomic Risk for Hormone-Sensitive Breast Cancer: Ignoring Valuable Data.” A useful and free online tool is the MD Anderson residual cancer burden (RCB) calculator.
For now, there isn’t a reliable test that can determine who can skip surgery altogether even if the cancer appears to melt away entirely in response to neoadjuvant therapy. But more isn’t always better and the flip side of the issue is the question of why so many women are having bigger surgeries than is necessary. More patients who qualify for lumpectomies are having mastectomies, even though lumpectomies are just as effective (even slightly more so) at reducing the risk of death from breast cancer. And the smaller surgeries can let women avoid the “Sophie’s choice” of breast reconstruction (with no great options and frequent complications), maintain sexual sensation, and recover more quickly.
There are many reasons why someone might chose a mastectomy that isn’t medically necessary, and these are deeply personal decisions. Some people choose mastectomies because they never felt all that comfortable in their bodies with breasts. Others want to avoid—or have logistical barriers to accessing—the radiation treatment that accompanies a lumpectomy. But it’s important that people who choose a mastectomy, because they think it’s the “safest” option most likely to ensure they’ll never get breast cancer again, have time with their providers to review the data and understand that survival outcomes are as good (and even slightly beter) for women who have a lumpectomy and radiation rather than a mastectomy.
[For more on this topic, see the blog post published earlier: “No Winners in Debate Over Treatment Options.”]
Medical advances are usually described as new treatments that let doctors do more for patients. But sometimes the real advance is in doing less—what’s called treatment de-escalation. Even though some surgery is still needed for invasive breast cancer, it’s no longer the central element for breast cancer treatment for most people.