Annals of Surgery Journal Club

Interactive resource for surgery residents and surgeons to discuss and critically evaluate articles published in Annals of Surgery selected by a monthly guest expert who will review an article each month, offer questions and respond to reader's comments.

Wednesday, April 6, 2016

April 2016 Journal Club

Moderator:

 

​​​​Dr Lee Gravatt Wilke is a Professor of Surgery at the University of Wisconsin School of Medicine and Public Health in Madison, Wisconsin.  She is the Director of the University of Wisconsin Breast Center and Interim Division Chair of the UW Section of General Surgery.  Dr Wilke is the Chair of the Research Committee for the American Society of Breast Surgeons and Board Member for the Alliance for Clinical Trials in Oncology.  Her primary interests include novel breast cancer clinical trials and translational breast cancer research. 


Featured Article:

Relationship Between Margin Width and Recurrence of Ductal Carcinoma In Situ:  Analysis of 2996 Women Treated with Breast Conserving Surgery for 30 years.  Van Zee KJ, et al.  ​

Summary:

Ductal Carcinoma In Situ or DCIS is a non invasive breast malignancy in which histologically malignant cells are detected within the mammary duct versus outside the basement membrane.  The diagnosis of DCIS occurs primarily through screening mammography and most commonly presents as microcalcifications.  In the past 30 years the incidence of DCIS has grown from insignificant to greater than 20% of the breast "cancer" cases, now accounting for more than 60,000 cases annually. [1] DCIS has recently been a focus of national media attention (Time Magazine October 2015) due to the frustration felt by providers and patients in understanding which DCIS events will actually lead to invasive disease and for whom the disease will remain indolent.  There is an active interest in the breast cancer community to identify biologic markers within DCIS which can better advise patients on their surveillance options to reduce overtreatment and identify those who should consider surgical and adjuvant therapies. 

Dr Van Zee and colleagues from Memorial Sloan Kettering have provided an important adjunct to the literature on DCIS. Through a retrospective review of a prospective database maintained at their institution, 2996 patients with DCIS between the years 1978 and 2010 were identified and a multi-variate model created to evaluate the influence of margin width (distance of DCIS from the edge of the resected tissue) and radiation therapy on breast cancer recurrence. Included in the model were factors that are also considered influential on recurrence; patient age, family history, clinical presentation, endocrine therapy, cancer grade and year of surgery.  Consistent with prior literature the authors report an overall recurrence rate of 12% (363/2996) of which approximately  ½ were invasive disease and ½ DCIS. The patient demographics described in this cohort included women of median age 57, the majority (65%) were post menopausal, 59.6% had low or intermediate grade DCIS and 43% had a 2nd surgery or re-excision. An important feature of this cohort is the fact that 46% did not undergo radiation following surgical excision.  Although the study was not randomized there was a sizeable group who did not receive post surgical radiation.   Fifteen percent of patients with positive margins experienced a recurrence while those with greater than 10mm margins had a 10.8% recurrence rate.  For those patients who did not receive radiation, wider margins was statistically significantly associated with a lower recurrence while those women who underwent radiation did not have an association between margin width and recurrence.  In the multivariate model only margin width, not age or tumor grade,  was associated with lower recurrence rates with sequentially lower hazard rates for recurrence with wider margins.  For those patients who did not receive radiation therapy, the link between margin width and recurrence was strong while for those patients undergoing radiation there was no association. 

Any retrospective study has limitations due to biases created from physician influence, patient preferences, time changes in treatment options offered  and competing medical co-morbidities.  Important however to note in this study is the fact that "in the worst" case for patients with positive margins and no radiation therapy there was only a 23.3% (crude) recurrence risk while women with radiation therapy and margins greater than 10mm had a 8.6% risk of recurrence.  Our ideal world would certainly be to identify those 8-20% of women who are at risk for recurrence and provide them with additional adjuvant therapy while offering the vast majority of patients either surgical removal alone and/or surveillance.  Drs Van Zee and Morrow have provided the breast community with important statistics to convey to our patients during the shared decision making discussion regarding the options for treatment of DCIS; highlighting the importance of margin width in those interested in avoiding radiation treatment.  Notable in all studies of DCIS is the fact that regional treatment of surgery and/or radiation does not influence survival.  Published in a similar time period was a 120,080 patient study of DCIS from SEER which showed that patients who undergo lumpectomy vs lumpectomy plus radiation vs mastectomy have similar disease free survival in the 98% range.[2]

 

The "horizon" for the DCIS therapy includes several important clinical studies which will help elucidate the importance of genomic characterization as well as the role of "active surveillance" for patients with low risk DCIS.  In the meantime we can use the data provided by Dr Van Zee to inform patients on the pros and cons of a second surgery vs radiation therapy. 

Questions:

  1. ​ The SSO and ASTRO recently published quidelines regarding recommendations for margin width for patients with invasive cancer;  recommending "no tumor on ink" as a standard  for patients with early stage disease who are undergoing breast conservation and whole breast radiation therapy.[3]  Is this consistent with the paper provided by Drs Van Zee and collegaues?  Can radiation obviate the need for obtaining "wider margins?"
  2. What are the consequences and or risks associated with the use of a re-excision to obtain wider margins vs radiation therapy?
  3. Should the breast cancer community consider a randomized trial assessing the use of <2mm vs >2mm margins for DCIS; for invasive breast cancer?
  4. What clinical trial recently completed accrual evaluating the use of "neoadjuvant" endocrine therapy for women with estrogen positive DCIS?

References:

1. Siegel R, Ma J , Zou Z et al. Cancer statistics, 2014. CA Cancer J Clin. 2014;64 (1):9–29 

2. Worni M, Akuskevich I, Greenup R et al.  Trends in Treatment patterns and Outcomes in DCIS. JNCI 2015; Sep30; 107.

3. Moran MS, Schnitt SJ, Giuliano AE, et al., 2014 Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole breast irradiation in stage I and II invasive breast cancer. Ann Surg Oncol 21:704–716