De-escalating Breast Cancer Treatment—Mission Forward

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 effort to eliminate surgery in an effort to reduce the burden of breast cancer care.  

As a breast cancer surgeon, I have a keen appreciation of the advantages and disadvantages of surgery. Depending on the patient’s unique circumstances, breast cancer surgery either can greatly enhance or greatly diminish the quality of life of a woman, often without improving overall survival. The art of medicine and surgery is to harmonize the treatment approach with anindividual 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 of treatment is intensified to improve cancer control.  However, increasingly this means de-escalating therapy, which means that the intensity and extent of therapy can be minimized to reduce the burden of therapy without compromising cancer control.      

Common examples of escalating therapy includes:

1. Adding radiation or chemotherapy after surgery based on new pathology detected in the tissue removed at the time of surgery;

2. Converting from mastectomy to lumpectomy when pathology results reviewed more extensive disease; or

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 more effective drug therapies, de-escalation of therapy is becoming increasingly more common. For example, I commonly use the following descalation therapies to reduce the burden of treatment 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-fraction or 30-fraction postoperative whole breast radiotherapy to target radiation to the tumor site while sparing health tissues the effects of radiation.

3. Preoperative chemotherapy or pre-operative anti-estrogen therapy, as appropriate, to reduce the extent of breast cancer and the extent of required surgery;

4. Cryoablation instead of surgical removal of selected cancers.

One of the greatest concerns raised by Drs. Morrow and Winer was that the effort to minimize the burden of surgery might leave some women with an elevated risk of recurrence and reduced overall survival.  Another common concern is that heightened surveillance (that is, more mammograms and more biopsies) that accompanies non-operative management of breast cancer canproduce such significant patient anxiety that possibly exceeds the physical trauma of surgery.  Though valid, these concerns should not deter our efforts toadjust our treatment approach based on the extent of disease and risk of disease recurrence, which included ongoing scientific efforts to figure out which individual cancers or 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 in the debate about reduce the need for surgery in selected cases.  Here, they really got it wrong or perhaps they haven’t been listening close enough.  

While it might not be the predominant viewpoint of women facing a breast cancer diagnosis, I have heard from maybe women who would option for a non-surgical approach if they could be confident that it could achieve comparable cancer control and survival. Completely missing in the article’s discussion of surgical de-escalation is the option of percutaneous ablation, such as 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.  Initially, I was quite reluctant to commit the time to research the topic and write a book chapter—after all, who actually reads textbooks? However, having completed the task, I am now convincedthat non-operative management of breast cancer in selected cases is a reasonable option for a subset of women looking to the avoid surgery.  The challenge for us as breast cancer researchers is to identity the most appropriate subset of women and circumstances in which non-operative management can be safely employed without compromising cancer control and patient survival.

As you already know, I am currently leading a multicenter, ongoing trial evaluating cryoablation as an alternative to surgery for stage one invasive breast cancer.  Thus far, preliminary findings are very promising.

As I write this post, I am also in the process of drafting a research protocol to examine the use of cryoablation for the management of stage 0 breast cancer or ductal carcinoma in situ (DCIS).  

The main aim of the DCIS-cryoablation study is to examine the use of cryoablation in the management of DCIS.  Although some patients elect to manage their DCIS with observation alone or observation plus Tamoxifen, one of the greatest ironies is breast cancer therapy is that DCIS (a condition that poses no direct risk to survival) is commonly treated more aggressively than invasive breast cancer, including an unacceptably high rate of mastectomy, a requirement for wider lumpectomy margins, and a high rate of reoperation.

Cryoablation can potentially serves as a compromise solution that balances the desire to disrupt the progression of DCIS toward invasive breast cancer while also minimizing the burden of wide excision, reoperation, and/or mastectomy.

The second aim of the DCIS 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 are a DCIS lesion might progress to invasive breast cancer, there is strong evidence that the immune microenvironment at the site of DCIS plays an important role in limiting disease progression from DCIS to microinvasive and invasive cancer. Thus, inducing a beneficial immune response with cryoablation might reduce the risk of DCIS progression to invasive breast cancer, the most endpoint of all DCIS therapies. Furthermore, understanding the immune response to cryoablation in DCIS might provide insights into 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, I am drawn to the challenge of expanding the options for breast cancer therapy to include cryoablation in appropriate patients.