ASCO, American Society for Radiation Oncology and Society for Surgical Oncology today issued an updated joint clinical practice guideline on the use of radiotherapy in women with breast cancer undergoing mastectomy.
The expert panel unanimously affirmed that the use of radiotherapy after mastectomy reduced the risks for locoregional failure, recurrence and breast cancer mortality in women with T1 or T2 breast cancer and up to three positive axillary nodes.
Bruce G. Haffty
However, the panel advised that the potential harms associated with radiotherapy might outweigh the benefits in patients with a low risk for recurrence.
Additionally, patients who elect to omit axillary dissection after a positive sentinel lymph node biopsy should only receive radiotherapy if sufficient evidence exists to justify its use, without further testing to determine if additional axillary nodes are involved.
“We still don’t have a single, validated formula that can determine who needs postmastectomy radiotherapy, but we hope that the research evidence summarized in this guideline update will help doctors and patients make more informed decisions,” Stephen B. Edge, MD, FACS, vice president of health care outcomes and policy and professor of oncology at Roswell Park Cancer Institute and professor of surgery at University of Buffalo, said in a press release. “We also hope that this publication will spur more research into patient and tumor characteristics that predict risk for recurrence after mastectomy.”
Strength of evidence
ASCO previously published expert guideline recommendations on the use of radiotherapy after mastectomy in 2001.
“The use of postmastectomy radiotherapy has been widely accepted for patients with four or more positive lymph nodes, but there is still controversy regarding the value of postmastectomy radiotherapy for those with one to three positive nodes,” the panelists wrote.
The current update addresses the use of radiotherapy in patients with one to three positive lymph nodes, as well as its use in patients undergoing neoadjuvant systemic therapy. The guidelines also
discuss the use of postmastectomy radiotherapy in women with T1 or T2 tumors and a positive sentinel lymph node biopsy who elect not to undergo axillary lymph node dissection.
A systemic review of 22 trials by Cancer Care Ontario served as the primary evidentiary basis for the guideline update. This review represented aggregated data from 8,135 women randomly assigned to receive or not receive radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery.
These data included 3,786 women who underwent axillary dissection and 1,133 women with one to three positive lymph nodes. The review found that in the latter cohort, the use of postmastectomy radiation significantly reduced the 10-year risk for locoregional failure (4.3% vs. 21%; P < .001).
Further, women who received radiotherapy had a lower 10-year risk for any recurrence (33.8% vs. 45.5%; P < .001) and 20-year breast cancer mortality (41.5% vs. 49.4%; P = .01; RR = 0.78).
However, questions remained regarding strategies to balance the possible adverse events associated with radiotherapy with the potential benefits.
“For many women, postmastectomy radiotherapy reduces the risk for local and regional failure, but physicians must weight this benefit with the considerable side effects associated with this treatment, Bruce G. Haffty, MD, FASTRO, professor of medicine at Rutgers Robert Wood Johnson Medical School, chairman and associate director of the Cancer Institute of New Jersey, and immediate past president of ASTRO’s Board of Directors, said in the release. “This cooperative guideline underscores the complexity inherent in decisions related to postmastectomy radiotherapy, as well as the importance of clinical judgment in treatment planning.”
Due to a high level of evidence-based data, the expert panel recommended unanimously that women with T1 or T2 tumors and one to three positive axillary lymph nodes receive postmastectomy radiotherapy.
However, there are potential factors that physicians and patients should take into account when deciding to pursue radiotherapy.
“Some subsets of patients are likely to have such a low risk for locoregional failure that the absolute benefit of postmastectomy radiotherapy is outweighed by its potential toxicities,” the panelists wrote. “In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend postmastectomy radiotherapy or not requires a great deal of clinical judgment.”
Physicians should account for factors that suggest a low recurrence risk. These decisions should also include consideration of patient characteristics — including older age (> 40-45 years); limited life expectancy due to mitigating factors, such as comorbidities; and the presence of coexisiting conditions that may increase the risk for complications — as well as pathologic findings and biologic characteristics.
Despite this, the panel did not officially identify any subgroups that should not undergo postmastectomy radiotherapy.
The decision to pursue postmastectomy radiotherapy should be made with input from clinicians in all involved disciplines, either through a formal tumor board or through referral, the panel wrote. They further noted that patients should be actively involved in the decision.
“In an era of personalized medicine, we want to be sure that we offer the right care to the right patients,” Abram Recht, MD, professor of radiation oncology at Harvard Medical School and deputy chief and senior radiation oncologist at Beth Israel Deaconess Medical Center, said in the release. “Thanks to advances in systemic therapy, fewer women need radiation therapy after mastectomy. This means we can be more selective when recommending this treatment to our patients.”
Further recommendations, future research
The panel issued a moderate recommendation that women with T1 or T2 tumors and a positive sentinel node biopsy, but who do not undergo axillary lymph node dissection, should only receive postmastectomy radiotherapy if there is sufficient evidence to justify its use without confirming the involvement of additional axillary nodes.
Additional recommendations included the use of postmastectomy radiotherapy for women with stage I or stage II cancer and axillary node involvement after neoadjuvant systemic therapy, and that radiation should be given to internal mammary glands and the supraclavicular axillary apical nodes — in addition to the chest wall or reconstructed breast — in women with positive axillary nodes.
However, radiation to these areas may result in additional toxicities, including pulmonary and cardiac morbidities, and the risks may outweigh the benefits among certain patients.
The development of new consensus guidelines has also served to identify areas in need of further research, according to Monica Morrow, MD, FACS, chief of breast surgery at Memorial Sloan Kettering Cancer Center.
“This guideline highlights the need to individualize therapy, as well as identifies areas where more research is needed,” Morrow said in the release. “It emphasizes that we are moving beyond a simplistic one-size-fits-all approach to more tailored therapy that will improve benefits for patients.” – by Cameron Kelsall
Disclosure: Morrow reports honoraria from Genomic Health. Recht reports institutional research funding from CareCore and U.S. Oncology and institutional research funding from Genomic Health. Edge reports no relevant financial disclosures. Please see the full study for a list of all other panelists’ relevant financial disclosures.