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Surgery and Metastatic Breast Cancer

7 June 2020

An abstract presented at last week’s virtual meeting of the American Society of Clinical Oncology focused on whether or not there is a benefit to surgery for the primary breast tumor in patients with metastatic, or Stage IV, breast cancer.

Metastatic breast cancer (Met-BC) is when the breast cancer spreads beyond the breast and underarm lymph nodes. Common sites of metastases include the lungs, liver, bones, and brain. Anyone diagnosed with breast cancer has the potential to develop metastatic disease, but approximately 5-10% of patients are found to have Met-BC at the time of initial diagnosis, known as de-novo Stage IV. For these patients, it has been controversial whether or not to recommend some form of breast surgery (lumpectomy or mastectomy) to remove the primary tumor. Some studies have shown a survival benefit when the primary tumor is removed, but widespread adoption of the results of these studies has been limited because in many of these studies, patients who underwent surgery were younger, healthier, and had a lower volume of metastatic disease compared with the general population of patients with Met-BC.

Dr. Seema Khan presented the results of the ECOG-ACRIN Research Group E2108 study. In this study, patients who had stable Met-BC (after 4-8 months of treatment) were randomized to either surgery or no surgery for the primary tumor. The two study groups were well-matched for age, race, and breast cancer subtype. With a median follow up of 59 months, there was no improvement in overall survival or in progression-free survival. Local progression (cancer continuing to grow in the breast) was more common in patients who did not undergo surgery (25.6 versus 10.2% at 3 years). At 18-month assessment, health-related quality of life was significantly worse in those who underwent surgery, but no differences were observed at the 6-month or 30-month assessment intervals.

During her presentation, Dr. Khan acknowledged that there may be situations where surgery for the primary tumor is a reasonable option in the setting of Met-BC. She noted that there is room for individualization, but stressed that as there is no survival benefit and no improvement in quality of life, surgery for the primary tumor in the setting of Met-BC should not routinely be performed. 

It is important to note that any medical meeting abstract, whether an oral presentation or poster, has been evaluated by the meeting program committee but has not been subject to rigorous peer review as would occur with a formal manuscript submission. Abstracts often do not include the full set of results, and additional findings may be included in the eventual publication, some of which may be different than those presented in the abstract. We look forward to the peer-reviewed publication when it is available. 

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Breast Conserving Therapy for Male Breast Cancer

30 June 2019

Note – if you would like a copy of the studies discussed below but are not able to access them from the journal website, please email me: contact at drattai dot com

In a study recently published in the Annals of Surgical Oncology, Bateni et al used the National Cancer Database to assess outcomes in patients with male breast cancer based on surgical therapy. The authors found improved 10-year survival in patients who underwent breast conserving therapy (BCT) which they defined as partial mastectomy (also called lumpectomy) plus radiation therapy.

Male breast cancer makes up about 1% of all new breast cancer diagnoses; approximately 2500 men are diagnosed in the US each year. Treatment guidelines for male breast cancer are similar to those for post-menopausal women despite growing evidence that breast cancer in men is a biologically different disease versus that in women. One of the challenges for clinical trials is the relatively small numbers of male breast cancer patients diagnosed each year. However, many clinical trials have not included men. 

A total of 8445 patients with stage I and II breast cancer, treated between 2004-2014, were included for analysis. 61% underwent mastectomy, and 18% underwent BCT. 12% had mastectomy with radiation, and 8% had partial mastectomy without radiation. Median follow up was 52 months. At 10 years, overall survival was as follows:

  • 74% BCT
  • 58% mastectomy
  • 56% mastectomy with radiation
  • 56% partial mastectomy without radiation

The image below is Figure IA from the manuscript, which show the “crude” overall survival for male breast cancer patients depending on surgical therapy.

Evaluating patients who had breast conservation with or without radiation, the authors noted that patients who were older, had higher tumor stage, higher cellular grade, and triple negative histology had poorer overall survival rates. They noted that there were differences in patient age, co-morbidities (other medical conditions), margin status and chemotherapy use for patients who underwent BCT versus partial mastectomy alone. However, after accounting for these differences, survival rates still favored BCT, suggesting that radiation therapy is an important component of improved outcomes. 

Limitations of the study noted by the authors include the retrospective nature, and the inability to understand some of the factors that influenced the decision for mastectomy versus breast conservation. Her2/neu status was not uniformly reported in the NCDB until 2010, so almost half of the patients in this study did not have this information. They also noted a larger percentage (4.9 vs 1.4%) of patients in the BCT group had triple negative breast cancer, which might explain why more of these patients were also treated with chemotherapy. It is also not clear how much of an influence the use of chemotherapy and endocrine therapy had in terms of the survival rates that were noted.

In a separate article, De La Cruz et al performed a systematic literature review of the studies evaluating breast conservation in men (excluding the Bateni et al study discussed above). The authors found 8 publications meeting their criteria. Among these studies, there were 859 patients who underwent breast conservation, 14.7% of all male breast cancer surgeries in the combined papers. Reporting on the “weighted average”, local recurrence (cancer returning in the breast) was 9.9%, disease-free survival was 85.6% and 5 year survival was 84.4%. As with the retrospective database analysis, there are limitations to this type of literature review – studies may use the same data points for inclusion, including use of radiation therapy, chemotherapy, and margin status. There may be significant differences in the patient populations in the various studies reviewed. As in the Bateni et al paper, there may be multiple unknown factors that influenced a decision for surgery type.

Men tend to present with larger tumors, especially relative to breast size, so often mastectomy is recommended. However, the authors of both papers were of the opinion that breast conservation is oncologically safe and a very reasonable option for men with early stage breast cancer, if they desire. Bateni et al stressed the importance of radiation therapy if breast conservation is utilized. Both papers highlight the importance of clinical trials for male breast cancer, so that treatment recommendations can be based on the best available evidence.

Additional information on Male Breast Cancer:

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(Reasonable) Fear Prompts “Extra” Mastectomy Decision

** 6 December 2018 – Editor’s Note:
The NSABP B-39 clinical trial results were recently presented at the San Antonio Breast Cancer Symposium. This study compared 3 forms of radiation therapy. After 10 year followup, approximately 4% of patients who underwent whole-breast irradiation after lumpectomy developed cancer recurrence in the same breast. This is lower than what was quoted below (10-15%, point #3) which was based on older data. This new study demonstrates that the recurrence rate after lumpectomy and radiation (4%) is nearly equivalent to that of mastectomy (1-3%).

3 June 2014

A study was recently published evaluating the reasons why women diagnosed with breast cancer might undergo a contralateral prophylactic mastectomy. First, some definitions:
–       Mastectomy – removal of the entire breast
–       Prophylactic mastectomy – removal of a breast that does not have cancer
–       Contralateral prophylactic mastectomy (CPM) – removal of the breast that does NOT have cancer, in a patient undergoing mastectomy for cancer on the other side

The study, which was published in JAMA Surgery, concluded that “Many women considered CPM and a substantial number received it, although few had a clinically significant risk of contralateral breast cancer. Receipt of magnetic resonance imaging at diagnosis contributed to receipt of CPM. Worry about recurrence appeared to drive decisions for CPM although the procedure has not been shown to reduce recurrence risk. More research is needed about the underlying factors driving the use of CPM.”

Some background information:
1.  Over 25 years’ worth of data exists showing that long-term survival is equivalent whether a woman undergoes a lumpectomy or a mastectomy:  In other words, you will not live any longer if your breast is removed.

2.  There is no difference in the likelihood of metastatic disease (spread outside the breast – most commonly bones, liver, lung and brain) whether you have a lumpectomy or mastectomy.

**see editor’s note, above. 
3.  Lumpectomy followed by radiation therapy (this is also called breast conservation therapy, or BCT) generally has low rates of “in breast recurrence” or “in breast new primary” – low rates of the original cancer coming back in the same breast, or a new cancer developing in the same breast.  These rates are historically about 10-15%, although these rates are likely reduced with modern adjuvant antihormonal, radiation, and chemo- therapies.

4.  Even though much more breast tissue is removed (~99% of breast tissue cells) mastectomy is still associated with a 1-3% risk of cancer recurrence at the site of breast removal.  This is usually in the skin or muscle.

5.  CPM is associated with a 20-40% complication rate, especially unplanned additional surgery

6.  The average woman’s risk of developing a new cancer in the opposite breast is approximately 0.5-1% per year. If a cancer develops in the contralateral (other) breast, it is considered a “new primary” – a whole new breast cancer. Even though it might be the same type as the original cancer, it is generally not considered a recurrence. If the original cancer is estrogen / progesterone receptor positive, taking tamoxifen or aromatase inhibitors can reduce the risk of cancer returning after a lumpectomy, and can reduce the risk of a new cancer developing in the other breast. However, lumpectomy or mastectomy for the original cancer does not alter the rate of new breast cancer development.

7.  Women who carry a BRCA gene mutation have a 60-80+% lifetime risk of developing breast cancer in either breast, and a high risk of developing a new breast cancer, so bilateral mastectomy is often recommended. These patients are generally excluded from the discussions regarding whether or not CPM is a reasonable option due to their extremely high risk.

Over the past 20 years, research studies have supported a “less is more” approach to breast cancer surgery such as: BCT,  narrower margins of normal tissue removed around cancer, and less extensive lymph node removal. Before instituting these changes, studies were done to ensure that less aggressive surgery does not impact long-term survival rates. Despite these advances, there has recently been a steady increase in the rate of mastectomy, as well as CPM.  In article after article, physicians are scratching their heads.  The use of MRI, inadequate education, unrealistic expectations from reconstructive surgery, the “celebrity effect”, as well as fear and anxiety have been blamed.

The “new” study and our thoughts:
The recent study in JAMA Surgery focused on a small subset of women (8%) from a national database that elected CPM as part of treatment for unilateral breast cancer.  The authors reported that of 106 patients who received CPM, “80% indicated it was done to prevent breast cancer from developing in the other breast,” leaving only 21 patients (1.5%) from their sample of 1447 surveyed women that elect CPM for reasons other than the prevention of the development of a new contralateral breast cancer.  However, the author’s conclusions ignore this and direct the reader’s attention instead to patients’ concern for recurrence, stating, again, that “worry about recurrence appeared to drive decisions for CPM.”

The problem with this type of analysis is this:  when ‘patient fear’ is discussed, it frequently is implied by the reporting media that hysterical women are running to the operating room to be unnecessarily operated on by uneducated surgeons.

Judging the merits of a surgical procedure or treatment on the fact that few women “are likely to experience a survival benefit,” is not reflective of the complexity of the treatment decision-making process for women with a new diagnosis of breast cancer.  Faced with a multitude of decisions to make in a short time frame, it is not surprising that many such patients will report anxiety concerning recurrence.

The truth is simple:  surgical choice is a combination of factors. There is little doubt that some physicians do not spend the time needed to hear the concerns of their patients and respond to them appropriately. Conversely, some patients do not want to hear all of the facts, preferring simply to opt for what seems the “safest” approach, even though the science says otherwise.

What we see in our offices is a rational fear: Many women understand that the type of surgery does not determine their survival.  While of utmost importance, survival is not the only thing that is important to women being treated for breast cancer. Women worry about having to repeat the whole process in another year or so if something new shows up on a mammogram or if a lump is felt. Women question the value of annual mammography for surveillance when their initial tumor was not picked up by a mammogram. Women have seen their family members and friends develop complications from radiation therapy and from attempts to perform additional surgery after radiation therapy. While women understand that a mastectomy is no guarantee that they will remain cancer-free, to many it is such a significant decrease in the rate of recurrence or new primary cancer that they feel it is an acceptable trade off for the complication rates that have been reported in patients who undergo a CPM with reconstruction.  Physicians also agonize over the decision.  Properly educated patients are in the best position to make decisions regarding their own breast health care, but even the best education does not alleviate all anxieties, nor can it eliminate all risk.

Physicians and researchers talk about the increasing rate of CPM as a crisis. But the real crisis is that at this point, we simply do not have options for women that they are comfortable with. Unnecessary surgery is a concern for patients and physicians. However, until we can look a woman in the eye and give her more accurate information about her individual risk of recurrence or new primary disease, it is our opinion that the decision for CPM should be between a woman, her family, and her physicians.

Additional Reading:
JAMA Editorial: Contralateral Prophylactic Mastectomy – An Opportunity for Shared Decision Making
Medscape Article – Misconceptions and Fear Prompt Contralateral Mastectomy
The Patient Perspective: Blog Post by Catherine Guthrie

Deanna J. Attai, MD
Michael S. Cowher, MD

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Misconceptions and Fears Prompt Contralateral Mastectomies

16 September 2013

The following article appeared in Medscape and covered a recent study suggesting that many women base their decision to undergo a mastectomy on fear. I was happy to contribute my thoughts to what is a very complex issue and a very difficult decision for so many women. ~DJA

Fran Lowry

Sep 16, 2013

Women with breast cancer, especially younger women, are choosing to have their healthy breast removed because of mistaken beliefs about the effectiveness of mastectomy and unfounded fears about the risks for contralateral disease.

In a cross-sectional survey of 123 women with early bilateral breast cancer who chose to undergo contralateral prophylactic mastectomy (CPM), the overwhelming majority cited improving their chances of survival (94%) and reducing the risk that cancer will develop in the other breast (98%) as their primary reasons for deciding to have the additional surgery.

The results appear in the September 17 issue of the Annals of Internal Medicine (Ann Intern Med. 2013;159:428-429).

Read more

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Surgery and Survival Rates – FOX 11 Interview

30 January 2013

A recent study in the journal Cancer compared patients with early stage breast cancer who underwent lumpectomy with radiation to patients who underwent mastectomy, and found that the patients who underwent lumpectomy had a better overall survival.

It is important to realize that this is an “observational study”, meaning the researchers went back to older data and analyzed the results – in the case of this study, they reported on patients treated between 1990-2004. There are many factors that were not accounted for, most importantly the specific subtype of cancer. It is not clear if the patients who underwent mastectomy had more aggressive tumors, which might in part explain the difference in survival rates.

Randomized clinical trials have demonstrated that the long-term survival is equivalent for patients undergoing a lumpectomy with radiation or mastectomy – in other words – you will not live any longer if the breast is removed. This is important to remember as more women are requesting mastectomy, and even removal of the healthy breast. While there are limitations to this current study, it at least reinforces the point that more surgery is not necessarily better.

The following interview discussed some of the history of breast cancer surgery as well as a discussion of the journal study:

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