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:

13 December 2016

A study published in the journal Cancer concluded that women with larger social networks have better breast cancer (BC) outcomes. In noting that large social networks predict lower overall mortality in healthy populations, the researchers analyzed a group of women who were already participating in four cohort studies. They evaluated associations between social networks within 2 years of a BC diagnosis and outcomes. Among 9267 women, there were 1448 recurrences and 1521 deaths. 990 of the deaths were due to breast cancer. In the patients studied, they noted that:

  • Socially isolated women were more likely to be Caucasian, college-educated and nulliparous (never had children)
  • Socially isolated women were less likely to be physically active and were more likely to be smokers, drink more than the recommended amount of alcohol, and be overweight
  • Women who were socially isolated were more likely to undergo lumpectomy and were less likely to receive chemotherapy and hormonal therapy
  • There were no associations between social isolation and age, menopausal status at diagnosis, cancer stage, and treatment with radiation

Regarding outcomes:

  • Women with smaller social networks had a higher risk of recurrence, BC specific mortality and overall mortality
  • Adjustments for lifestyle and treatment factors attenuated the associations with recurrence and mortality, but the associations remained statistically significant
  • Social network associations with recurrence and breast cancer specific mortality were stronger for patients with Stage I and II BC  compared to Stages III and IV
  • Associations between social networks and outcomes did not differ based on age, time since diagnosis, ER/PR status, Her2/neu status, or treatment
  • Being “unmarried / unpartnered” was associated with worse BC specific and overall mortality for older but not younger white women or non-white women (any age)
  • Community ties predicted lower risk of BC specific and overall mortality in older white and Asian women but not in other groups
  • Religious participation was not associated with outcomes

So what to make of this study and these findings? The first point to make is that this study notes associations, or correlations – not cause and effect. Cause and effect cannot be determined from this type of cohort study, and a randomized controlled trial to assess the relationship between social networks and breast cancer outcomes would be impossible. While the authors attempted to control for many variables, the study population was not representative of the average US breast cancer population. In addition, there was no assessment of the quality of the social networks, a point I raised in a interview regarding the study.

Cancer treatment is challenging even for those with a large supportive social network. No one should have to feel they are going it alone – there are many resources for help and support, but you may need to ask (hard to do for many independent women!). However, if you are one of those women (like me) who keeps her social network very small, this study should not prompt more worry during an already stressful time.

Correlation does not equal causation, by Lisa Simpson:

6 October 2015

As we’ve learned more about tumor biology, and as our treatments have improved, the question of whether or not early detection is still important has been raised. Tumor stage has historically been the most important factor in determining overall prognosis. The earlier cancer is detected, the better the survival rates. As we’ve gained a better understand the various breast cancer subtypes, we’ve learned that some patients with early stage breast cancer have a poor survival rate, and some patients who are diagnosed at later stages do quite well. This is the effect of tumor biology. Stage has to do with tumor size and whether or not there has been spread to the lymph nodes or other areas of the body. Tumor biology reflects just what are those little cells up to – do they have innately indolent or aggressive behavior.

In recent years, because of the increased knowledge of the importance of tumor biology, there has been much discussion regarding the value of screening mammography as well as cancer overdiagnosis and overtreatment. If tumor biology is king, then does the stage of diagnosis really matter?

A study recently published in the British Medical Journal concludes that tumor stage is still important. Dr. Sepideh Saadatmand and colleagues tapped into the Nationwide Netherlands Cancer Registry. They evaluated data from the registry focusing on female breast cancer patients diagnosed between 1999-2005 and 2006-2012. Nearly 174,000 cases were analyzed.

They demonstrated a 17% increase in the diagnosis of breast cancer between the 2 time periods, some of which they proposed was related to an aging society, as increasing age is associated with breast cancer development. They found that in women treated during 2006-2012, tumors were smaller, less likely to be associated with positive lymph nodes, and were of lower grade. These women were also more likely to be treated with chemotherapy, hormonal therapy, and targeted therapy. Significant findings were that regardless of what year the patients received treatment, patients with increasing tumor size (in patients with tumors larger than 1cm) and those with positive lymph nodes had a worse prognosis. Limitations of the study include: 1.) Follow up for the 2nd group of patients is relatively short, and 2.) As this was a database analysis, information about other medical conditions that may impact use of screening as well as overall mortality was not available.

The goal of breast cancer screening is to detect tumors in earlier stages, which should lead to improved survival rates. In an editorial accompanying the BMJ study, Dr. Harold Burstein from the Dana Farber Cancer Institute in Boston noted that screening mammography rates in the Netherlands approaches 80% and he attributes a high rate of screening as well as coordinated multidisciplinary care to their improved survival rates. It’s not time to give up on screening mammography and early detection just yet. But it’s also important to realize that early detection may not always lead to improved survival, due to the effects of tumor biology.

12 November 2013

Over the past year, breast cancer and mastectomy has been in the spotlight due to attention from celebrities such as Angelina Jolie and Amy Robach.

There is no question that when public figures share their stories, awareness is raised. The unfortunate part is that important facts are usually omitted from the conversation, and misinformation is spread. While anyone has the right to discuss their disease, public figures should be held to a different standard. Their information reaches millions, and their words are held as truth. Unfortunately, we rarely if ever have the complete story. Most often, an announcement is made about upcoming or recent surgery, and statements are made about “beating cancer” or “being cured”. In the absence of information about the pathology report, stage of disease and other factors, these statements do nothing to educate or inform. I would not expect anyone, including someone in the public eye, to disclose their medical records. However a simple statement such as “I am choosing this treatment with the advice of my physicians” can go a long way towards acknowledging that the treatment decisions are complex and unique to the individual.

Some important points:
– Early detection does not equal cure. Some breast cancers are so aggressive that they will go on to metastasize regardless of how early they were found. Some breast cancers will never metastasize, even if they become quite large. Tumor biology – the behavior of the individual cells – is more important than the size of the tumor at diagnosis. Statements such as “a mammogram saved my life” do not apply to every breast cancer case.

– You will not live any longer if you have your breast removed. The survival rates from breast cancer are the same whether you undergo a lumpectomy with radiation or a mastectomy. Statements such as “I had a mastectomy because I’m young and wanted to be aggressive” have no basis in reality. You can be appropriately aggressive by having a lumpectomy followed by radiation, depending on the extent of your tumor. More surgery is not better.

– Breast cancer can come back even after the breast has been removed – the risk is approximately 1-5%. After lumpectomy and radiation, the risk of cancer retuning in the breast is approximately 5-10% with modern techniques. Statements such as “I had a mastectomy so I don’t have to worry about cancer anymore” also has no basis in reality. With either surgery (lumpectomy or mastectomy), there is a risk of cancer metastasizing, or showing up somewhere else in the body. Any invasive breast cancer has the potential to shed cells from the main tumor into the bloodstream. Those malignant cells may then form tumors in other areas of the body, such as the bones, lungs, liver, and brain. The type of surgery (lumpectomy versus mastectomy) does nothing to reduce the risk of metastatic disease, and the survival rates are equal regardless of the surgery performed.

– In patients who undergo removal of the ovaries (due to the increased risk of ovarian cancer), there still is a slight risk of developing ovarian or primary peritoneal cancer, which mimics ovarian cancer in it’s growth and aggressiveness. Patients who have had breast cancer or are BRCA mutation carriers are also at increased risk for the development of cancers in addition to breast and ovarian, so lifelong surveillance is important.

– Many have the misconception that if they undergo a mastectomy, they will not require chemotherapy. Chemotherapy is given based on the tumor stage as well as tumor biology – the decision is made on the aggressiveness of the cancer. As mentioned above, a mastectomy does not prevent the cancer from spreading, so chemotherapy may still be required after mastectomy.

– Radiation therapy is utilized after lumpectomy to reduce the risk of cancer returning in the breast. While radiation is generally not needed after mastectomy, there are some cases where it is required. Similar to the decision for chemotherapy, the decision for post-mastectomy radiation depends on the stage of disease and tumor biology.

– The recovery from surgery is not always straightforward and most patients are not “back to a normal life” a few days after surgery. As with any surgery, there can be unexpected complications and additional procedures may be needed.

– Reconstructive techniques, while much improved, can never guarantee a perfectly natural or symmetric result. Reconstruction after mastectomy is a much different operation than undergoing implants for cosmetic purposes. Once the breast has been removed, it can never be replaced. The skin (and nipple if preserved) are numb, and the feel and appearance are different. Many patients are very happy with the cosmetic results of their reconstruction, but realistic expectations are needed.

– In regards to BRCA genetic testing, some women struggle tremendously with the decision even to be tested. There are implications not only for the patient but also for her relatives. In patients who test positive for a mutation, there are also difficult decisions to be made regarding surveillance versus prophylactic surgery.

There’s Another Side to the Amy Robach Breast Cancer Story is an excellent post by Gary Schwitzer of the HealthNewsReview on the subject.