This month’s newsletter draws attention to a recent JAMA Oncology editorial,
De-escalating Breast Cancer Surgery—Where is the Tipping Point (Dec 12, 2019), in which respected surgeons, Monica Morrow and Eric Winer, discussed the pros but mostly the cons of de-escalating breast cancer surgery, in reference to ongoing clinical trials to reduce the burden of breast cancer care by eliminating surgery whenever possible.
As a breast cancer surgeon, I have a keen appreciation for the advantages and disadvantages of surgery. Depending on the patient’s unique circumstances, breast cancer surgery can either greatly enhance or greatly diminish a woman’s quality of life--often without improving her long-term survival. The art of medicine and surgery is to harmonize the treatment approach with an individual patient’s goals and tumor characteristics in a way that maintains or improves cancer control while preserving or enhancing quality of life. At times, this could mean escalating therapy, which means that the extent and intensity of treatment is increased to optimize cancer control. In other instances, increasingly optimizing care means de-escalating therapy, which minimizes the intensity and extent of therapy to reduce the burden of therapy without compromising cancer control.
Common examples of escalating therapy include:
1. Adding radiation and/or chemotherapy after surgery based on findings detected in the tissue removed during surgery;
2. Converting from lumpectomy to mastectomy when pathology results from surgery reveal disease not treatable with lumpectomy; and
3. Removal of all underarm lymph nodes if cancer is found in one or more nodes.
Due to more frequent detection of smaller cancers and a better understanding of cancer biology, de-escalation of therapy is becoming increasingly more common. For example, I commonly use the following de-escalation approaches to reduce treatment burden and expedite recovery:
1. Lumpectomy combined with breast reduction or breast lift instead of bilateral mastectomy and reconstruction to improve cancer removal, maintain breast symmetry and improve overall breast appearance;
2. Single dose Intraoperative partial breast radiotherapy instead of 16-dose or 30-dose postoperative whole breast radiotherapy to target radiation to the tumor site while sparing the surrounding tissues the side effects of radiation;
3. Pre-operative chemotherapy or pre-operative anti-estrogen therapy, as appropriate, to reduce the extent of breast cancer in the breast and nodes to reduce the extent of surgery;
4. More frequent use of anti-estrogen pills for cancers that in the past would have been treated with chemotherapy; and
5. Cryoablation or tumor freezing instead of surgical removal of selected cancers.
One of the major concerns raised by Drs. Morrow and Winer was that the effort to minimize the burden of surgery might leave some women with inadequately treated cancers and reduced long-term survival. Another significant concern is that the need for more frequent mammograms and/or biopsies following non-operative management of breast cancer can produce such significant patient anxiety that the emotional trauma of avoiding surgery might exceed the trauma of surgery.
Valid though it may be, the cautionary tone of the editorial should not diminish our efforts to continually adjust our treatment approach based on an individual patient’s extent of disease and expanding knowledge of which tumors are more likely to grow, spread, and recur.
Another point of significant disagreement is Dr. Morrow’s and Dr. Winer’s view that the voice of the patient has been excluded from the debate about de-escalating therapy. Here, they demonstrate a clear misunderstanding of changing times or perhaps they simply haven’t been listening close enough. While a de-escalation treatment approach may not be the predominant goal of women facing a breast cancer diagnosis, I constantly hear from women in search of less invasive and less disfiguring breast cancer treatment options. However, the greater problem is that many patients are completely unaware of the de-escalation options like the ones described above. For example, missing for the editorial’s discussion of surgical de-escalation is the option of cryoablation, which addresses many of the concerns raised by Drs. Morrow and Winer.
I was recently invited to write a chapter for a surgical textbook on non-surgical management of breast cancer, including percutaneous ablation (e.g., cryoablation) and use of anti-estrogen therapy alone in selected cases. Initially, I was quite reluctant to commit the time to research the topic and write the book chapter—after all, who actually reads textbooks? However, having completed the task, I am now convinced that non-operative management of breast cancer is a reasonable option for subsets of women with suitable cancers. The challenge for us as breast cancer researchers is to identity the most appropriate subset of women and circumstances for which non-operative management can be safely offered without compromising long-term and cancer control and survival.
As you may already know, I am currently leading an ongoing, multicenter clinical trial evaluating cryoablation as an alternative to surgery for women with early stage invasive breast cancer. Thus far, preliminary findings are very promising. As I write this post, I am also in the process of authoring a clinical trial to examine the use of cryoablation for the management of non-invasive breast cancer or ductal carcinoma in situ (DCIS). In the lifespan of a cancer, DCIS (Stage 0) is typically the step that precedes the development of an invasive breast cancer (Stage 1-4). However, in up to 40% of women, DCIS never progresses any further. Although most women with DCIS are advised by their doctors to receive surgery, radiation, and Tamoxifen to prevent the development of invasive breast cancer, one of the greatest ironies in the field of breast cancer therapy is that DCIS (a condition that poses no direct survival risk) is frequently treated more aggressively than invasive breast cancer, including an unacceptably high rate of mastectomy for DCIS, a requirement for wider lumpectomy margins, and a higher rate of reoperation compared to invasive cancer.
Cryoablation can potentially serve as a compromise solution that balances the desire to prevent the development of DCIS into invasive breast cancer while also eliminating the burden of lumpectomy, reoperation, and/or mastectomy for a condition that is typically non-life-threatening.
The second aim of the DCIS-cryoablation study is to determine if cryoablation is capable of stimulating a beneficial immune response in women with DCIS. Although multiple factors may influence if and when DCIS progresses to invasive breast cancer, there is now strong evidence that immune cells environment at the site of DCIS may either inhibit or in some cases encourage the development of invasive breast cancer. This is where the purported immune cryoablation might be most helpful. If cryoablation truly is capable of stimulating a beneficial anti-cancer immune response, in might help to keep DCIS from developing into invasive breast cancer, which is the main goal of surgery, radiation, and all the other things we do to treat DCIS. Additionally, knowledge of the immune response to cryoablation of DCIS might identify ways to reduce the risk of recurrence of invasive breast cancer.
As a breast cancer surgeon, I earn my living by performing surgery on breast cancer patients, as outlined above. As a breast cancer researcher and patient advocate, I am drawn to the challenge of expanding the options for breast cancer therapy beyond surgery to include cryoablation in appropriate patients. I am encouraged by the early results of ongoing cryoablation studies, but there is still much work to do to establish a role for cryoablation in the management of breast cancer.
Want to learn more about cryoablation and how it is currently being utilized to expand treatment options for women?
Author
Dennis R. Holmes, M.D.
