American College Of Surgeons - Inspiring Quality: Highest Standards, Better Outcomes

CRP Investigator Webinar: Breast (A011106 and AFT-25)

A Surgical Investigators Meeting Webinar focusing on Ongoing Breast Cancer Cooperative Group Clinical Trials.

Sponsored by the ALLIANCE/American College of Surgeons Clinical Research Program.

Access the recording

Recorded Wednesday, January 10

Presentation Slides

Moderator: Judy C. Boughey, MD, FACS Education Committee, ACS CRP

Speakers:  Marilyn Leitch, MD, FACS; Cynthia Ma, MD; Shelley Hwang, MD, MPH, FACS

Trials Covered: A011106 and AFT-25


Alternate approaches for clinical stage II or III Estrogen Receptor positive breast cancer Neoadjuvant Treatment (ALTERNATE) in postmenopausal women

The study is being conducted to determine whether neoadjuvant endocrine therapy with fulvestrant or the combination of anastrozole and fulvestrant, is better than anastrozole when given before surgery to shrink the cancer. Anastrozole inhibits tumor growth by reducing the levels of estrogen and has been approved by the Food and Drug Administration (FDA) of the United States for use after surgery for postmenopausal women with estrogen receptor positive breast cancer. It is also considered a standard of care to give anastrozole for a few months before surgery to shrink the tumor. Fulvestrant inhibits tumor cell growth by reducing the levels of estrogen receptor in the tumor cell. It is not approved by the FDA for use in women with early stage breast cancer before or after surgery, but is approved by the FDA for patients with advanced (Stage 4) estrogen receptor positive breast cancer that has spread to other parts of the body.

Key Inclusion Criteria

  • Postmenopausal women
  • Clinical T2-T4c, any N, M0 invasive breast cancer
  • Invasive breast cancer is ER+ with an Allred score of 6, 7, or 8 and HER2 negative
  • Must agree to undergo the required research biopsies at baseline, week 4 and at surgery.

Exclusion Criteria

  • An excisional biopsy of this breast cancer
  • Surgical axillary staging procedure prior to study entry [Note: FNA or core needle biopsy of axillary node is permitted]
  • Treatment for this cancer including surgery, radiation therapy, chemotherapy, biotherapy, hormonal therapy or investigational agent prior to study entry
  • History of invasive breast cancer or contralateral DCIS
  • Multifocal invasive breast cancer (defined as >5cm between invasive lesions)

A011106 Schema

ALTERNATE Trial Schema

Estimated enrollment: 1,455

Start date: December 2013

End date: April 2019


Comparison of Operative to Monitoring and choice of Endocrine Therapy (COMET) Trial for Low Risk DCIS: A Phase III Prospective Randomized Trial

The COMET Trial is designed to assess outcomes with a less aggressive approach to the management of DCIS, and to continue to advance the knowledge regarding the biologic behavior of DCIS.

COMET is a prospective randomized trial that will assess the risks and benefits associated with active surveillance (AS) versus guideline concordant care (GCC) for patients with low-risk DCIS (Figure 1). The overarching hypothesis of the study is that management of low-risk DCIS using an active surveillance approach (without surgical resection) does not yield inferior oncologic or quality of life outcomes when compared with guideline concordant care (which includes surgical resection of the DCIS +/- radiation).

COMET Trial Schema

COMET Trial Schema

Patients in the active surveillance group will be followed with mammography every six months to assess for invasive progression. The guideline concordant care group will be treated with surgery, radiation, or a combination according to usual care guidelines. Endocrine therapy will be optional in both groups. 

Inclusion in the COMET Trial will be limited to women ages 40 and older who present with a new diagnosis of DCIS grades I/II. DCIS must be estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive. If human epidermal growth factor receptor 2 (HER2) testing is performed, the DCIS must be HER2 0, 1+, or 2+ by immunohistochemistry (IHC). Male patients, patients with bloody nipple discharge, pregnant patients, or patients with documented history of prior tamoxifen, aromatase inhibitor, or raloxifene use will be excluded. Results from this study will help to determine whether de-escalation of treatment for low-risk DCIS is a feasible approach, and how clinical outcomes and quality of life compare between treatment and surveillance groups.

This trial will recruit 1,200 patients at 100 sites and is open for enrollment. 

About the Speakers and Program

More about Marilyn Leitch, MD

A. Marilyn Leitch is professor of surgery at UT Southwestern Medical Center. Dr. Leitch completed her fellowship in surgical oncology at MD Anderson Cancer Center in Houston in 1986. At UT Southwestern, Dr. Leitch has spearheaded the establishment of the Center for Breast Care. As a national leader in breast cancer research, Dr. Leitch serves on the Breast Oncology Local Disease Committee for the National Cancer Institute (NCI) and is a member of the board of directors for the Alliance for Clinical Trials in Oncology, one of the nation’s foremost NCI cooperative groups for cancer research.

More about Cynthia Ma, MD, PhD

Cynthia Ma is a medical oncologist and specializes in breast cancer. Dr. Ma is an associate professor in the division of oncology at the Washington University in St. Louis, with a research interest focused on identifying treatment resistance mechanisms and the development of novel therapeutic agents for the treatment of breast cancer. She is the clinical director of the breast program in the section of medical oncology and a member of the Alliance Breast Committee.

More about Shelley Hwang, MD

Shelley Hwang is chief of breast surgery and professor and vice chair of research at Duke University where she leads basic science, translational, and clinical research activities in early stage and in situ breast cancer.  She serves as a member of the NCI Breast Cancer Steering Committee and the NCCN Breast Cancer Screening and Diagnosis Panel.

More about Judy C. Boughey, MD, FACS, Education Committee, ACS CRP

Judy C. Boughey is professor of surgery and vice chair for research in the department of surgery and medical director of clinical research in the department of surgery. Dr. Boughey is the program director for the Multidisciplinary Breast Surgery Fellowship at Mayo. She is chair of the Publications Committee for the American Society of Breast Surgeons and Chair of the Education Committee for the American College of Surgeons Clinical Research Program. Dr. Boughey has led multiple national clinical trials funded by National Cancer Institute; ACOSOG Z1071 evaluating SLN surgery in patients with node positive breast cancer treated with neoadjuvant chemotherapy, ACOSOG Z11102 evaluating breast conservation in women with multiple ipsilateral breast tumors and ALLIANCE A11202 comparing axillary dissection to axillary radiation for patients with node positive disease after neoadjuvant chemotherapy. 

More about ALLIANCE/ACS Clinical Research Program

The mission of the ALLIANCE/American College of Surgeons Clinical Research Program (ACS CRP) is to reduce the impact of cancer by increasing knowledge and awareness of new evidence and practice standards; increasing the participation of community oncology surgeons in cancer research and cancer care activities; developing and implementing evidence-based practices in surgical oncology; and creating opportunities for meaningful health services research.