By Dr. Deanna J. Attai

I attended the 32^nd Annual Miami Breast Cancer Conference, held from February 26 – March 1, 2015. The following are some of the highlights from the conference that will be discussed during the #BCSM tweet chat on Monday 3/16/15.

Less surgery is better:
Many patients and even some physicians have the misconception that more surgery results in better outcomes. 2 presentations addressed this topic. Dr. Stuart Schnitt, a Professor in the Department of Pathology at Harvard Medical School in Boston, MA and the director of Anatomic Pathology at Beth Israel Deaconess Medical Center reviewed the data on breast conservation. Over 20 years of follow up from randomized clinical trials has demonstrated no improvement in survival in patients undergoing mastectomy compared to lumpectomy. However, there has been no universal agreement on what constitutes an adequate surgical margin (the rim of normal tissue around a tumor) in patients undergoing lumpectomy. In fact, he quoted a study where no single margin threshold width was identified as adequate by more than 50% of respondents. In addition, the re-excision (reoperation) lumpectomy rate for positive or close margins ranges from 0-70% across the country. One reason for this wide range in re-excision rates is that some surgeons will recommend additional surgery in order to get 2mm, 5mm or even larger margins. When there are no guidelines, you get a wide variety in practice.

The Society of Surgical Oncology and the American Society of Radiation Oncology (SSO-ASTRO) convened a multidisciplinary panel, which published this guideline recommending that “no ink on tumor” is an appropriate margin in patients with invasive cancer (ductal and lobular) undergoing lumpectomy. [When the surgeon removes the breast tumor, the surgeon or pathologist “paint” the tissue with different colors of ink, marking the different margins. When the pathologist looks at the tissue under the microscope, a standard part of the report is measuring the distance of the tumor from the closest margin. “Ink on tumor” is when they see ink right on the cancer cells]. 

We know that certain subgroups of patients have higher rates of local recurrence (cancer returning in the breast), including women younger than 40, and those with more aggressive biologic subtypes such as triple negative breast cancer. However, wider margins in these patients do not result in lower recurrence rates. Dr. Kelly Hunt, Professor and Chief, Surgical Breast Section of Breast Surgical Oncology at the University of Texas MD Anderson Cancer Center in Houston, TX reinforced the fact that widely clear margins do not reduce local recurrence rates in these patient populations.

The point was also made that consensus guidelines are an attempt to help standardize practice, but are not a substitute for clinical judgment; in selected circumstances, wider margins may be appropriate. But the important take-home message is that more surgery is not better. Ask your surgeon about their re-excision rates – an acceptable rate is <20%. If your surgeon recommends re-excision, ask why. There may be reasons where additional surgery is appropriate, but it a very reasonable question to ask.

Lymphedema:
Approximately 20% of women treated for breast cancer will develop lymphedema. Dr. Sarah McLaughlin is an Associate Professor of Surgery in the Section of Surgical Oncology and Program Director of the General Surgery Residency at the Mayo Clinic in Jacksonville, Florida, and she noted that identification of early lymphedema is important – when untreated, even mild swelling will progress to more severe forms in 50% of patients. Early intervention may reverse swelling, resulting in improvement in the patient’s quality of life, as well as cost savings.

Unfortunately, we still have not been able to predict with certainty which patients are at risk for developing lymphedema. Ongoing surveillance including measurement of the contralateral (opposite) arm is important because upper extremity volume fluctuates with weight changes and other factors – the unaffected arm will serve as the patient’s “control”.

She cited a study where after one year of follow up, the rate of lymphedema in women receiving intervention involving education, manual lymphatic drainage, scar massage and progressive range of motion shoulder exercises was 7% compared to 25% in those who received only education. The benefit of exercise, which can reduce the number and severity of exacerbations, was stressed.

Interest in surgical treatment of lymphedema is increasing, but results are very variable. Pre-emptive surgical techniques include axillary reverse mapping, prophylactic lymphovenous anastomosis, and combined autologous reconstruction with lymph node transfer. These techniques are currently undergoing extensive evaluation.
OncLive: Early intervention essential for proper lymphedema management

Genetic panel testing:
Dr. Pat Whitworth, Director of the Nashville Breast Center in Nashville, TN, presented on genetic panel testing. We’ve moved beyond BRCA 1/2 in terms of genetic testing. Many companies now offer what is called panel testing- with one sample, multiple genes can be tested. The problem is that for many of these genes, we do not always have a good idea of the subsequent breast cancer risk – many of the genes identified are associated with much lower rates of breast cancer development compared to patients with BRCA mutations.

When BRCA testing first became available in 1996, many patients were told that they had a “variant of unknown significance” (VUS). With more women being tested, a large number of VUS were identified, but over time, data were generated to categorize a VUS either as deleterious (associated with an increased risk of breast cancer development) or insignificant. In 2002, the rate of VUS in African American women was 40%; currently it is <5%.

Many questions remain about panel testing, the most important being clinical value. Detection of a mutation or VUS does not necessarily convey an increased risk of breast cancer, and the results need to be taken in the context of the patient’s family history. Informed consent and cost effectiveness are also important considerations. Patients as well as physicians that care for them need to be educated about the less common mutations and VUS, so that unnecessary surgeries do not occur.

Obesity Inflammation: The Breast Cancer Link
Dr. Clifford Hudis, Past-President of the American Society of Clinical Oncology, Chief of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center, and Professor of Medicine at Weill Cornell Medical College in New York, NY presented on the growing public health challenge of obesity. Obesity increases the risk for a number of illnesses, and likely will replace tobacco as leading modifiable risk factor for development of many common malignancies. The average American currently consumes approximately 20% more calories today compared to 1950, and increasing body mass index has become a global problem .

Obesity is associated with an increased incidence of post-menopausal breast cancer. Factors include insulin resistance, inflammatory cytokines, and an estrogen effect. Obesity causes a microscopic inflammatory state. With the release of inflammatory mediators, there is an increase in the level of aromatase, which is the enzyme that converts precursors to estrogen. Lifestyle adjustments can help reduce the breast cancer risk by modifying the inflammatory reaction to obesity.
OncLive: Hudis highlights interplay between inflammation, obesity, and breast cancer

Tumor Heterogeneity:
Dr. George Sledge, Professor of Oncology at Stanford University Medical Center in Palo Alto, CA, presented on tumor heterogeneity. We have known for some time that there are many different subtypes of breast cancer, and that a cancer in one individual may be made of up different cell populations – this is referred to as tumor heterogeneity. This can make it difficult to treat breast cancer, as this heterogeneity can sometimes be hard to recognize. Dr. Sledge discussed how we need a better understanding of tumor heterogeneity and improved methods for testing, but that this presents many challenges. For example, one study that he cited noted that some cancers may have as many as 40 different cancer genes, present in 73 combinations. Many had multiple “driver mutations” – mutations that need to be targeted due to their importance in the cancer’s growth. Adding to the challenge is that metastatic lesions may not be the same as the primary lesion. Some of the differences between the primary and metastatic cancer are related to the therapy – for example, treatment of the primary with endocrine therapy may lead to resistance in the metastatic lesion. Clinical trials are ongoing, especially in regards to immunotherapy, to try to work around the complex inner workings of the cancer cell.
OncLive: Heterogeneity complicates treatment decisions in breast cancer

Immunotherapy:
Dr. Elizabeth Mittendorf, an Associate Professor of Surgical Oncology and Deputy Chair of Research at The University of Texas MD Anderson Cancer Center in Houston, TX, presented an update on immunotherapy strategies. She discussed the important role that the immune system plays in the development of cancer. She described mechanisms of cancer “immunoediting”, consisting of elimination, equilibration, and escape as well as areas of ongoing research.

Additional Information:
Dr. Lisa Carey – Treating triple negative breast cancer
Dr. Debu Tripathy – Possibility of curing metastatic breast cancer
Dr. Hyman Muss – Optimizing treatment in older breast cancer patients
Dr. Deanna Attai – The doctor will tweet with you now

 Transcript from 3/16/15 Chat