A review of more than 50 studies (many randomized controlled trials) concluded that surgery and radiation therapy “remain standard-of-care treatment options” in the management of ductal carcinoma in situ.1 The review continues the widely reported discussion on managing ductal carcinoma in situ, prompted by the publication this past year of an observational study looking at data from 108,196 women diagnosed with ductal carcinoma in situ.2 Both studies were published in JAMA Oncology.
Narod et al2 found that among women diagnosed with ductal carcinoma in situ, “the risk of death increases after a diagnosis of an ipsilateral second primary invasive breast cancer, but prevention of these recurrences by radiotherapy does not diminish breast cancer mortality at 10 years.” This led some to question the need for treatment aimed at preventing recurrence. (The study and some reactions to it were reported in the October 10, 2015, issue of The ASCO Post.) According to the recent review, “While the value of radiation therapy following lumpectomy has been questioned, the data continue to support its use to reduce the risk of local recurrences.”
‘Can’t Jump From Active to Passive Treatment’
Active treatment remains the standard of care in the management of ductal carcinoma in situ at this time. And while reducing the treatment duration and making it less toxic is imperative, we can’t jump from active treatment to passive without further study.— Chirag Shah, MD
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The review study’s lead author, Chirag Shah, MD, a radiation oncologist at the Cleveland Clinic Taussig Cancer Institute, told The ASCO Post that the review “will basically reinforce what has been seen in previous trials, as well as in evidence-based guidelines—Active treatment remains the standard of care in the management of ductal carcinoma in situ at this time. And while reducing the treatment duration and making it less toxic is imperative, we can’t jump from active treatment to passive without further study.”
In the review article, Dr. Shah and his colleagues maintained “there is a lack of level 1 evidence or prospective evidence to support the widespread adoption” of more conservative approaches to managing ductal carcinoma in situ, without surgery or radiation. Dr. Shah reiterated that point during his interview with The ASCO Post but noted some other “concerning” factors as well. “We have randomized data showing that women who develop invasive recurrences after treatment have higher rates of breast cancer mortality. So even the data we do have suggest we have to be cautious.”
Unable to Identify Low-Risk Cohort
According to the review article, “no cohort of patients has yet to be identified (based on patient, pathologic, or treatment criteria and/or tumor genetics) that does not benefit from adjuvant radiation to some extent with respect to local control.”
The inability of clinical and pathologic characteristics to identify a low-risk cohort of patients who receive no local control benefit from adjuvant therapy has prompted investigation of other means of identifying these patients. For instance, multigene expression assays have been evaluated, but in two studies cited in the review, local recurrence still exceeded 10% in the low-risk subsets identified.
“Some data are coming out with invasive breast cancers and looking at something not as intensive as a multigene assay but still looking at tumor genetics to see if we can identify the lowest-risk patients,” Dr. Shah noted. “However, it was a small set of patients with luminal A breast cancer, suggesting they may not need radiotherapy. It does require further validation.”
The search continues for a reliable way to identify a low-risk cohort of patients with ductal carcinoma in situ who would not benefit from adjuvant radiation. “We are not there yet,” admitted Dr. Shah.
Alternative Radiation Strategies
As a result of the inability to identify low-risk subsets of patients who do not receive a local control benefit from adjuvant whole breast irradiation, “alternative strategies to standard whole breast irradiation have altered the treatment landscape, allowing the ability to maximize local control while limiting the duration of adjuvant radiation therapy to 1 to 3 weeks,” the review authors reported.
Hypofractionated whole-breast irradiation “is now considered a gold standard,” Dr. Shah stated, estimating that 50% to 60% of ductal carcinoma in situ cases are treated with accelerated whole-breast irradiation in his practice.
“Hypofractionationated radiation therapy has been shown now in four randomized trials to be equivalent to standard whole-breast irradiation and is the growing standard of care in node-negative women,” Dr. Shah revealed. He acknowledged that three of the four studies did not include patients with ductal carcinoma in situ, “but most clinicians feel very comfortable extrapolating from early-stage breast cancers to ductal carcinoma in situ.” A Canadian study published in 2014 did include patients with ductal carcinoma in situ.3 Among 1,609 patients treated for ductal carcinoma in situ, local control was improved with hypofractionated whole-breast irradiation (89% vs 86% with standard whole-breast irradiation; P = .03).3
“Accelerated whole-breast irradiation represents an excellent alternative to standard whole-breast irradiation if patients meet appropriate technical and treatment factors based on evidence-based guidelines (age > 50 years, no chemotherapy, maximum whole-breast dose < 107% of prescription),” Dr. Shah and his coauthors wrote in the review article. “There is a large national push to offer accelerated hypofractionated whole-breast irradiation to most women who are candidates,” Dr. Shah added.
The use of accelerated partial-breast irradiation—targeting the lumpectomy cavity and a surrounding margin of tissue—is evolving. “I would say that while hypofractionated irradiation is completely mainstream,” Dr. Shah commented, “partial breast irradiation still has a little ways to go before being completely mainstreamed.”
Tumor Bed Boosts
“As the use of oncoplastic techniques continue to expand, a challenge for radiation oncologists is identifying the lumpectomy cavity or tissue at risk for a tumor bed boost,” according to the review article. “This is of clinical importance because a tumor bed boost has been shown to reduce rates of local recurrence with invasive cancers as well as with ductal carcinoma in situ. Furthermore, the absolute benefit of a tumor bed boost on local control is greatest among younger women.”
“Traditional radiation has consisted of whole-breast radiation, where we treat the whole breast and then often a tumor bed boost,” Dr. Shah explained. This is based on two large randomized trials,4,5 which compared boost and no boost and found a reduction in local recurrence with the addition of the boost.” The tumor boost was given “where the tumor was taken out, using the seroma as a surrogate,” he continued. “But when we perform oncoplastic surgery, we are often moving tissue around, and the seroma may not be a surrogate for where the lumpectomy was done or may not present. So we are having to find now ways to do tumor bed boosts so we can give the younger patients the benefit of that and be accurate with our delivery.”
Endocrine Therapy Questioned
The authors also noted that recent observational studies have led to suggestions of new approaches consisting of biopsy and confirming ductal carcinoma in situ “with no further upfront treatment other than endocrine therapy (in some cases) with subsequent clinical and mammographic surveillance.” Such concepts were considered “hypothesis-generating,” but they “neither represent level 1 evidence nor do they support off-protocol use of such approaches,” the authors wrote.
“A new question to be asked,” according to the review article authors, “is whether radiation therapy alone following surgery is a more appropriate option than endocrine therapy.” Citing concerns about high rates of noncompliance with endocrine therapy and the 5 or more years of treatment required, the authors added, “in light of recent data suggesting limited long-term benefit of tamoxifen in preventing invasive local recurrences and questions on whether the benefit of endocrine therapy on local control is limited to patients with positive margins, while understanding the potential for an increased risk of contralateral breast cancers with omitting endocrine therapy” is important.
Projects to address this question “are not underway yet, but that is where we are headed,” Dr. Shah shared. The objectives are “twofold,” he explained. “One is to look at clinical outcomes and quality of life, and the other is to look at the cost-effectiveness of such an approach, basically adding radiation in and taking endocrine therapy out.” ■
Disclosure: Dr. Shah reported no potential conflicts of interest.
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