Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer.

BACKGROUND: Adjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information. METHODS: We performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A-subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years. RESULTS: Of 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1). CONCLUSIONS: Among women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829.).

Disruptions in Cancer Care Due to the COVID-19 Pandemic and Fear of Cancer Recurrence in Women with Breast Cancer: A Mixed-Methods Study.

OBJECTIVE: This study investigated if fear of cancer recurrence (FCR) levels and the proportion of women having a clinical level of FCR differed by whether women had or had not experienced disruptions in their cancer tests and treatments due to the pandemic. METHODS: We conducted a mixed-methods study between November 2020 and March 2021 among women diagnosed with breast cancer in the previous five years at the time of their entry in the study. Women completed a questionnaire online assessing disruptions in breast cancer tests and treatments due to the pandemic and the severity subscale of the Fear of Cancer Recurrence Inventory. Semi-structured interviews were also conducted with a subsample of 24 participants and were thematically analyzed. RESULTS: The proportion of patients with a clinical level of FCR was significantly higher among those who experienced the postponement or cancellation of diagnostic and disease progression tests (e.g., blood tests, X-rays, or magnetic resonance imaging; adjusted PR = 1.27 95% CI = 1.13-1.43). Qualitative findings suggest that FCR was exacerbated by the pandemic context. In particular, perceived or actual barriers to care access due to the pandemic were identified as significant FCR-enhancing factors. CONCLUSIONS: These results highlight the need to keep diagnostic and progression tests as timely as possible to prevent increases in FCR levels and offer counselling about FCR when postponing or cancellation are inevitable.

OPAR: A Randomized Trial of Partial Breast Irradiation in Five Fractions Once Daily for Early Breast Cancer.

PURPOSE: Previous studies suggest that external-beam partial breast irradiation (PBI) delivered twice a day can lead to increased adverse cosmesis (AC). The objective of our trial was to determine whether two regimens for PBI given once daily over 1 week resulted in acceptable AC to inform a phase III trial. METHODS: Patients age ≥50 years with invasive breast cancer or ductal carcinoma in situ, ≤3 cm in size treated by lumpectomy with negative axillary nodes were randomly assigned to external-beam PBI of 30 Gy or 27.5 Gy, each given in five fractions once daily. The primary outcome was AC (fair or poor) by photographic assessment at 2 years. Secondary outcomes included AC assessed by nurse at 2 years, by patient self-assessment at 3 years, and late toxicity. On the basis of a 17% risk of AC with whole-breast irradiation, the upper bound of a two-sided 90% CI, 23% was set as the tolerance margin (OPAR, ClinicalTrials.gov identifier: NCT02637024). RESULTS: In total, 142 patients were randomly assigned to 30 Gy and 139 to 27.5 Gy. The median follow-up was 5 years. The mean age was 65 years, and the mean tumor size was 1.2 cm. Both schedules met acceptability criteria by photographic assessment (AC, 12.1% [90% CI, 8.2 to 17.6] for 30 Gy and 15.2% [90% CI, 10.8 to 21.1] for 27.5 Gy) and by nurse assessment. AC by patient self-assessment exceeded the 90% CI for the 30 Gy regimen. At 5 years, 16 (11.3%, 90% CI, 7.6 to 16.4) patients treated with 30 Gy and eight (5.8%, 90% CI, 3.3 to 9.9) patients treated with 27.5 Gy were observed to have grade 2 or more late toxicity. CONCLUSION: According to the study design, 30 Gy and 27.5 Gy resulted in acceptable cosmetic outcomes. In light of recent studies, a lower dose was chosen for the phase III trial.

Hypofractionated radiation therapy for breast ductal carcinoma in situ.

PURPOSE: Conventional radiation therapy (RT) administered in 25 fractions after breast-conserving surgery (BCS) is the standard treatment for ductal carcinoma in situ (DCIS) of the breast. Although accelerated hypofractionated regimens in 16 fractions have been shown to be equivalent to conventional RT for invasive breast cancer, few studies have reported results of using hypofractionated RT in DCIS. METHODS AND MATERIALS: In this multicenter collaborative effort, we retrospectively reviewed the records of all women with DCIS at 3 institutions treated with BCS followed by hypofractionated whole-breast RT (WBRT) delivered in 16 fractions. RESULTS: Between 2003 and 2010, 440 patients with DCIS underwent BCS followed by hypofractionated WBRT in 16 fractions for a total dose of 42.5 Gy (2.66 Gy per fraction). Boost RT to the surgical bed was given to 125 patients (28%) at a median dose of 10 Gy in 4 fractions (2.5 Gy per fraction). After a median follow-up time of 4.4 years, 14 patients had an ipsilateral local relapse, resulting in a local recurrence-free survival of 97% at 5 years. Positive surgical margins, high nuclear grade, age less than 50 years, and a premenopausal status were all statistically associated with an increased occurrence of local recurrence. Tumor hormone receptor status, use of adjuvant hormonal therapy, and administration of additional boost RT did not have an impact on local control in our cohort. On multivariate analysis, positive margins, premenopausal status, and nuclear grade 3 tumors had a statistically significant worse local control rate. CONCLUSIONS: Hypofractionated RT using 42.5 Gy in 16 fractions provides excellent local control for patients with DCIS undergoing BCS.

Quality-of-life measurement in randomized clinical trials in breast cancer: an updated systematic review (2001-2009).

BACKGROUND: Quality-of-life (QOL) measurement is often incorporated into randomized clinical trials in breast cancer. The objectives of this systematic review were to assess the incremental effect of QOL measurement in addition to traditional endpoints (such as disease-free survival or toxic effects) on clinical decision making and to describe the extent of QOL reporting in randomized clinical trials of breast cancer. METHODS: We conducted a search of MEDLINE for English-language articles published between May-June 2001 and October 2009 that reported: 1) a randomized clinical trial of breast cancer treatment (excluding prevention trials), including surgery, chemotherapy, hormone therapy, symptom control, follow-up, and psychosocial intervention; 2) the use of a patient self-report measure that examined general QOL, cancer-specific or breast cancer-specific QOL or psychosocial variables; and 3) documentation of QOL outcomes. All selected trials were evaluated by two reviewers, and data were extracted using a standardized form for each variable. Data are presented in descriptive table formats. RESULTS: A total of 190 randomized clinical trials were included in this review. The two most commonly used questionnaires were the European Organization for Research and Treatment of Cancer QOL Questionnaire and the Functional Assessment of Cancer Therapy/Functional Assessment of Chronic Illness Therapy. More than 80% of the included trials reported the name(s) of the instrument(s), trial and QOL sample sizes, the timing of QOL assessment, and the statistical method. Statistical power for QOL was reported in 19.4% of the biomedical intervention trials and in 29.9% of the nonbiomedical intervention trials. The percentage of trials in which QOL findings influenced clinical decision making increased from 15.2% in the previous review to 30.1% in this updated review for trials of biomedical interventions but decreased from 95.0% to 63.2% for trials of nonbiomedical interventions. Discordance between reviewers ranged from 1.1% for description of the statistical method (yes vs no) to 19.9% for the sample size for QOL. CONCLUSION: Reporting of QOL methodology could be improved.

Altered fractionation: rationale and justification for whole and partial breast hypofractionated radiotherapy.

Over the last 2 decades, we have seen major advances in the application of radiotherapy after breast-conserving surgery. Two important contributions are the use of whole-breast hypofractionation and accelerated partial-breast irradiation. Three large randomized trials comparing whole-breast hypofractionation versus conventional fractionation for early breast cancer have shown similar rates of local recurrence and morbidity. As a result, whole-breast hypofractionation is now an option for selected patients after breast-conserving surgery. The delivery of accelerated partial-breast irradiation (APBI) has been studied using techniques of multicatheter interstitial brachytherapy, balloon-based brachytherapy, external-beam radiotherapy, and intraoperative radiotherapy. Multiple single and multi-institutional data have been published indicating good long-term results with APBI (in highly selected, low-risk patients) in terms of tumor control and toxicity. However, the long-term results of large, phase III trials comparing APBI with whole-breast irradiation are still pending.

Use of axillary deodorant and effect on acute skin toxicity during radiotherapy for breast cancer: a prospective randomized noninferiority trial.

PURPOSE: To prospectively determine the effect of deodorant use on acute skin toxicity and quality of life during breast radiotherapy (RT). METHODS AND MATERIALS: Before breast RT, 84 patients were randomly assigned to the deodorant group (n = 40) or the no-deodorant group (n = 44). The patients were stratified by axillary RT and previous chemotherapy. Toxicity evaluations were always performed by the principal investigator, who was unaware of the group assignment, at the end of RT and 2 weeks after completion using the Radiation Therapy Oncology Group acute skin toxicity criteria. Symptoms of acute skin toxicity (i.e., discomfort, pain, pruritus, sweating) and quality of life were self-evaluated. For each criterion, the point estimate of rate difference with the 95% one-sided upper confidence limit was computed. To claim noninferiority owing to deodorant use, the 95% one-sided upper confidence limit had to be lower than the noninferiority margin, fixed to 12.8%. RESULTS: In the deodorant vs. no-deodorant groups, Grade 2 axillary radiodermatitis occurred in 23% vs. 30%, respectively, satisfying the statistical criteria for noninferiority (p = .019). Grade 2 breast radiodermatitis occurred in 30% vs. 34% of the deodorant vs. no-deodorant groups, respectively, also satisfying the statistical criteria for noninferiority (p = .049). Similar results were observed for the self-reported evaluations. The deodorant group reported less sweating (18% vs. 39%, p = .032). No Grade 3 or 4 radiodermatitis was observed. CONCLUSION: According to our noninferiority margin definition, the occurrence of skin toxicity and its related symptoms were statistically equivalent in both groups. No evidence was found to prohibit deodorant use (notwithstanding the use of an antiperspirant with aluminum) during RT for breast cancer.