Metaplastic carcinoma of the breast: matched cohort analysis of recurrence and survival.

PURPOSE: Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer, defined as mammary carcinoma with squamous or mesenchymal differentiation, that may include spindle cell, chondroid, osseous, or rhabdomyoid differentiation patterns. The implications of MBC recurrence and survival outcomes remains unclear. METHODS: Cases were ascertained from a prospectively maintained institutional database of patients treated from 1998 to 2015. Patients with MBC were matched 1:1 to non-MBC cases. Cox proportional-hazards models and Kaplan-Meier estimates were used to evaluate outcome differences between cohorts. RESULTS: 111 patients with MBC were matched 1:1 with non-MBC patients from an initial set of 2400 patients. Median follow-up time was 8 years. Most patients with MBC received chemotherapy (88%) and radiotherapy (71%). On univariate competing risk regression, MBC was not associated with locoregional recurrence (HR = 1.08; p = 0.8), distant recurrence (HR = 1.65; p = 0.092); disease-free survival (HR = 1.52; p = 0.065), or overall survival (HR = 1.56; p = 0.1). Absolute differences were noted in 8-year disease-free survival (49.6% MBC vs 66.4% non-MBC) and overall survival (61.3% MBC vs 74.4% non-MBC), though neither of these reached statistical significance (p = 0.07 and 0.11, respectively). CONCLUSION: Appropriately-treated MBC may exhibit recurrence and survival outcomes that are difficult to distinguish from those of non-MBC. While prior studies suggest that MBC has a worse natural history than non-MBC triple-negative breast cancer, prudent use of chemotherapy and radiotherapy may narrow these differences, although studies with more power will be required to inform clinical management. Longer follow-up among larger populations may further elucidate the clinical and therapeutic implications of MBC.

Breast conservation among older patients with early-stage breast cancer: Locoregional recurrence following adjuvant radiation or hormonal therapy.

BACKGROUND: For patients with breast cancer undergoing breast-conserving surgery (BCS), adjuvant radiation (RT) and hormonal therapy (HT) reduce the risk of locoregional recurrence (LRR). Although several studies have evaluated adjuvant HT ± RT, the outcomes of HT versus RT monotherapy remain less clear. In this study, the risk of LRR is characterized among older patients with early-stage breast cancer following adjuvant RT alone, HT alone, neither, or both. METHODS: This study included female patients from the Memorial Sloan Kettering Cancer Center (New York, New York) who were aged ≥65 years with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) T1N0 breast cancer treated with BCS. The primary endpoint was time to LRR evaluated by Cox regression analysis. RESULTS: There were 888 women evaluated with a median age of 71 years (range, 65-100 years) and median follow-up of 4.9 years (range, 0.0-9.5 years). There were 27 LRR events (3.0%). Five-year LRR was 11% for those receiving no adjuvant treatment, 3% for HT alone, 4% for RT alone, and 1% for HT and RT. LRR rates were significantly different between the groups (P < .001). Compared with neither HT nor RT, HT or RT monotherapy each yielded similar LRR reductions: HT alone (HR, 0.27; 95% CI, 0.10-0.68; P = .006) and RT alone (HR, 0.32; 95% CI, 0.11-0.92; P = .034). Distant recurrence and breast cancer-specific survival rates did not significantly differ between groups. CONCLUSIONS: LRR risk following BCS is low among women aged ≥65 years with T1N0, ER+/HER2- breast cancer. Adjuvant RT and HT monotherapy each similarly reduce this risk; the combination yields a marginal improvement. Further study is needed to elucidate whether appropriate patients may feasibly receive adjuvant RT monotherapy versus the current standards of HT monotherapy or combined RT/HT.

Salvage of locally recurrent breast cancer with repeat breast conservation using 45 Gy hyperfractionated partial breast re-irradiation.

PURPOSE: Mastectomy has long been the preferred approach for local salvage of recurrent breast cancer following breast-conservation therapy (BCT). Growing interest in avoiding mastectomy prompted RTOG 1014, a landmark phase two study demonstrating the feasibility of repeat BCT using a novel radiotherapy (RT) regimen (i.e., 45 Gy administered in 30 fractions of 1.5 Gy twice-daily to the partial breast, "rePBI"). We adopted this regimen as our institutional standard and report our observations regarding the safety and efficacy of rePBI as salvage therapy. METHODS: All patients at our institution who underwent repeat BCT and subsequently received rePBI from 2011 to 2019 were identified. Clinicopathologic features and treatment characteristics for both primary breast cancers and recurrences were collected, as were rates of subsequent recurrence and treatment-associated toxicities. RESULTS: The cohort included 34 patients with a median age of 65.8 (46.2-78.2) at the time of rePBI. At a median follow-up of 23.5 months, there were two subsequent locoregional recurrences (2-year local control rate 97%). There was no grade ≥ 3 toxicity. The most common acute toxicity (< 3 months) was radiation dermatitis (100%), and common grade 1-2 late toxicities (> 3 months) included fibrosis in 14 (41%), breast asymmetry in 12 (35%), and chest wall pain in 11 (32%). CONCLUSIONS: Repeat breast conservation using the hyperfractionated partial breast RT regimen defined by RTOG 1014 (45 Gy administered in 30 1.5 Gy twice-daily fractions) appears effective and well tolerated. No grade 3 or higher toxicities were observed and local control was excellent. Longer term follow-up among larger cohorts will define whether salvage mastectomy should remain the preferred standard.

Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial.

BACKGROUND: Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation. METHODS: We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181. FINDINGS: Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5-11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94-1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7-5·7) in the APBI group versus 3·9% (3·1-5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group. INTERPRETATION: APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women. FUNDING: National Cancer Institute, US Department of Health and Human Services.

Breast journal 2020 special issue: Post-mastectomy radiation: Tracking changes in the standard of care over 25 years.

This is an invited review article, tracking the changes in the indications and use of post-mastectomy radiation over the last 25 years. While radiation after mastectomy has been in use for decades, several key prospective randomized trials published in recent years have changed and strengthened role of this modality. This manuscript will track the milestones over the last three decades.

A dosimetry study of post-mastectomy radiation therapy with AeroForm tissue expander.

PURPOSE: To evaluate the dosimetric effects of the AeroFormTM (AirXanpders®, Palo Alto, CA) tissue expander in-situ for breast cancer patients receiving post-mastectomy radiation therapy. METHODS AND MATERIALS: A film phantom (P1) was constructed by placing the metallic canister of the AeroForm on a solid water phantom with EBT3 films at five depths ranging from 2.6 mm to 66.2 mm. A breast phantom (P2), a three-dimensional printed tissue-equivalent breast with fully expanded AeroForm in-situ, was placed on a thorax phantom. A total of 21 optical luminescent dosimeters (OLSDs) were placed on the anterior skin-gas interface and the posterior chest wall-metal interface of the AeroForm. Both phantoms were imaged with a 16-bit computed tomography scanner with orthopedic metal artifact reduction. P1 was irradiated with an open field utilizing 6 MV and 15 MV photon beams at 0°, 90°, and 270°. P2 was irradiated using a volumetric modulated arc therapy plan with a 6 MV photon beam and a tangential plan with a 15 MV photon beam. All doses were calculated using Eclipse (Varian, Palo Alto, CA) with AAA and AcurosXB (AXB) algorithms. RESULTS: The average dose differences between film measurements and AXB in the region adjacent to the canister in P1 were within 3.1% for 15 MV and 0.9% for 6 MV. Local dose differences over 10% were also observed. In the chest wall region of P2, the median dose of OLSDs in percentage of prescription dose were 108.4% (range 95.4%-113.0%) for the 15MV tangential plan and 110.4% (range 99.1%-113.8%) for the 6MV volumetric modulated arc therapy plan. In the skin-gas interface, the median dose of the OLSDs were 102.3% (range 92.7%-107.7%) for the 15 MV plan and 108.2% (range 97.8-113.5%) for the 6 MV plan. Measured doses were, in general, higher than calculated doses with AXB calculations. The AAA dose algorithms produced results with slightly larger discrepancies between measurements compared with AXB. CONCLUSIONS: The AeroForm creates significant dose uncertainties in the chest wall-metal interface. The AcurosXB dose calculation algorithm is recommended for more accurate calculations. If possible, post-mastectomy radiation therapy should be delivered after the permanent implant is in place.

Radiation Therapy After Breast-Conserving Surgery in Women 70 Years of Age and Older: How Wisely Do We Choose?

BACKGROUND: Despite data from randomized trials supporting omission of radiation therapy (RT) for women ≥ 70 years of age with T1, estrogen receptor-positive (ER+) tumors undergoing breast-conserving therapy (BCT), RT usage remains high. We reviewed our institutional experience to determine if risk factors for local recurrence or comorbidities influenced use. METHODS: Women ≥ 70 years of age with T1, ER+, human epidermal growth factor receptor 2-negative (HER2-) tumors undergoing BCT in 2010-2012 were identified from a prospectively maintained database. Ten-year estimated mortality was calculated using the Suemoto index. The associations of clinicopathological features and mortality risk on receipt of RT were examined. RESULTS: Overall, 323 patients with 327 cancers were identified. Median age was 75 years, median tumor size was 1 cm, and all were clinically node negative; 53.7% of patients received RT. RT usage decreased with age (73.6%, age 70-74 years; 49.5%, age 75-79 years; 33.3%, age 80-84 years; 10.7%, ≥ 85 years; p < 0.001). Within age groups, estimated mortality did not impact RT usage. On multivariable analysis, only younger age and larger tumor size were associated with RT use. Recurrence-free survival was 98% versus 93% with and without RT, respectively (p = 0.011). Those who received adjuvant radiation also had improved overall survival (92% vs. 89%), although this effect did not reach statistical significance (p = 0.051). CONCLUSION: Neither the factors associated with risk of local recurrence nor the estimated risk of death in 10 years were associated with use of adjuvant radiation in a large cohort of women ≥ 70 years of age with small ER+ breast cancers treated with breast-conserving surgery.

Delay in radiotherapy is associated with an increased risk of disease recurrence in women with ductal carcinoma in situ.

BACKGROUND: The current study was conducted to examine the association between ipsilateral breast tumor recurrence (IBTR) and the timing of radiotherapy (RT) in women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS). METHODS: Women with DCIS who were treated with BCS and RT from 1980 through 2010 were identified from a prospectively maintained database. IBTR rates, measured from the time of RT completion, were compared between those who initiated RT ≤8 weeks, >8 to 12 weeks, and >12 weeks after the completion of surgery. The association between RT timing and IBTR was evaluated by Kaplan-Meier and log-rank analyses; Cox modeling was used for multivariable analysis. RESULTS: A total of 1323 women met the inclusion criteria. The median follow-up was 6.6 years, with 311 patients followed for ≥10 years. A total of 126 IBTR events occurred. Patients were categorized by RT timing: 806 patients (61%) with timing of ≤8 weeks, 386 patients (29%) with timing of >8 to 12 weeks, and 131 patients (10%) with timing >12 weeks. The 5-year and 10-year IBTR rates were 5.8% and 13.0%, respectively, for RT starting ≤8 weeks after surgery; 3.8% and 7.6%, respectively, for RT starting >8 to 12 weeks after surgery; and 8.8% and 23.0%, respectively, for an RT delay >12 weeks after surgery (P = .004). On multivariable analysis, menopause (hazard ratio [HR], 0.54; P = .0009) and endocrine therapy (HR, 0.45; P = .002) were found to be protective against IBTR, whereas a delay in RT >12 weeks compared with ≤8 weeks was associated with a higher risk of IBTR (HR, 1.92; P = .014). There was no difference in IBTR noted between RT initiation at ≤8 weeks and initiation at >8 to 12 weeks after BCS (P = .3). CONCLUSIONS: A delay in RT >12 weeks is associated with a significantly higher risk of IBTR in women undergoing BCS for DCIS. Efforts should be made to avoid delays in starting RT to minimize the risk of disease recurrence. Cancer 2018;124:46-54. © 2017 American Cancer Society.

Impact of an In Situ Component on Outcome After In-Breast Tumor Recurrence in Patients Treated with Breast-Conserving Therapy.

BACKGROUND: Among all in-breast tumor recurrences (IBTR) following breast-conserving therapy (BCT), some comprise metachronous new primaries (NPs) while others are true recurrences (TRs). Establishing this distinction remains a challenge. METHODS: We studied 3932 women who underwent BCT for stage I-III breast cancer from 1998 to 2008. Of these, 115 (2.9%) had an IBTR. Excluding patients with inoperable/unresectable recurrences or simultaneous distant metastases, 81 patients with isolated IBTR comprised the study population. An IBTR was categorized as an NP rather than a TR if it included an in situ component. The log-rank test and Kaplan-Meier method were used to evaluate disease-free survival (DFS) and overall survival (OS), and univariate and multivariate analyses were performed using Cox proportional hazards regression models. RESULTS: At a median of 64.5 months from IBTR diagnosis, 28 of 81 patients had DFS events. Five-year DFS was 43.1% in the TR group (p = 0.0001) versus 80.3% in the NP group, while 5-year OS was 59.7% in the TR group versus 91.7% among those with NPs (p = 0.0011). On univariate analysis, increasing tumor size, high grade, positive margins, lymphovascular invasion, node involvement, lack of axillary surgery, chemotherapy, radiation therapy, and IBTR type (TR vs. NP) were significantly associated with worse DFS. Controlling for tumor size and margin status, TRs remained significantly associated with lower DFS (hazard ratio 3.717, 95% confidence interval 1.607-8.595, p = 0.002). CONCLUSION: The presence of an in situ component is associated with prognosis among patients with IBTR following BCT and may be useful in differentiating TRs and NPs.

Breast Cancer, Version 4.2017, NCCN Clinical Practice Guidelines in Oncology.

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

NCCN Guidelines Insights: Breast Cancer, Version 1.2017.

These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor-positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org.

Invasive Breast Cancer Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This article outlines the NCCN Guidelines specific to breast cancer that is locoregional (restricted to one region of the body), and discusses the management of clinical stage I, II, and IIIA (T3N1M0) tumors. For NCCN Guidelines on systemic adjuvant therapy after locoregional management of clinical stage I, II and IIIA (T3N1M0) and for management for other clinical stages of breast cancer, see the complete version of these guidelines at NCCN.org.

The Effect of Molecular Subtype and Residual Disease on Locoregional Recurrence in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy and Postmastectomy Radiation.

BACKGROUND: The relative contribution of biologic subtype to locoregional recurrence (LRR) in patients treated with neoadjuvant chemotherapy (NAC), mastectomy, and postmastectomy radiotherapy (PMRT) is not clearly defined. METHODS: 233 patients with stages 2 and 3 breast cancer who received NAC, mastectomy, and PMRT between 2000 and 2009 were included: 53 % (n = 123) had HR+ (ER or PR+/HER2-), 23 % (n = 53) had HER2+ (HER2+/HR+ or HR-), and 24 % (n = 57) had triple-negative (TN) disease (HR-/HER2-). The 5-year LRR rates were estimated by Kaplan-Meier methods. Cox regression analysis was performed to evaluate covariates associated with LRR. RESULTS: The median follow-up period was 62 months. A pathologic complete response (pCR) was seen in 14 % of the patients. The 5-year LRR rate was 8 % for the entire cohort. The LRR rate was 0 % for the patients with a pCR versus 9 % for the patients without a pCR (p = 0.05). TN disease [Hazard ratio (HR) 4.4; p = 0.003] and pathologic node positivity (HR 9.8; p = 0.03) were associated with LRR. Patients with TN disease had a higher LRR rate than patients with HER2+ or HR+ disease (20 vs. 6 and 4 %; p = 0.005). Among patients without a pCR, TN subtype was associated with increased LRR risk (26 versus 7 % HER+ and 4 % HR+; p < 0.001). CONCLUSIONS: Patients with TN breast cancer had the highest LRR rate after NAC, mastectomy and PMRT. Whereas no LRR was observed among TN patients with a pCR, TN patients with residual disease had a significantly higher LRR risk. Patients with HR+ and HER2+ breast cancer had favorable LRR rates regardless of NAC response, likely due to receipt of adjuvant systemic targeted therapies.

The Effect of Adjuvant Trastuzumab on Locoregional Recurrence of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Treated with Mastectomy.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpression was associated with locoregional recurrence (LRR) in the preadjuvant trastuzumab era. This study aimed to examine the effect of trastuzumab on LRR in mastectomy patients and whether it varied with postmastectomy radiation (PMRT). METHODS: From the authors' institutional database, 501 women with stages I-III HER2-positive breast cancer who underwent mastectomy from 1998 to 2007 were identified. A landmark analysis was performed to compare two cohorts: 170 women who received trastuzumab and 281 who did not. Kaplan-Meier methods were used to estimate locoregional recurrence-free survival (LRRFS). A propensity score analysis was used to balance the treatment groups with respect to multiple covariates. Analogous methods were used to study the effect of PMRT. RESULTS: The women in the trastuzumab group were more likely to be node positive and to receive systemic therapy or PMRT (p < 0.01). The 5-year LRRFS was 98 % in the trastuzumab troup versus 94 % in the no trastuzumab group [hazard ratio (HR) 0.31; 95 % confidence interval (CI) 0.09-1.09; p = 0.07]. After adjustment for multiple covariates, including receipt of chemotherapy and PMRT, trastuzumab decreased LRR rates (HR 0.21; 95 % CI 0.04-0.94; p = 0.04). Among the women who received PMRT, trastuzumab reduced the 5-year LRR rate (0 vs 5 %; p = 0.06). Among those who did not receive PMRT, trastuzumab did not significantly decrease LRR (3 vs 6 %; p = 0.26). CONCLUSION: High rates of locoregional control (5-year rate, 98 %) were observed among patients who received trastuzumab and mastectomy ± PMRT. Trastuzumab decreased LRR in HER2-positive women who received mastectomy and PMRT, suggesting that the largest benefit is seen in a higher-risk subset of patients.

NCCN Guidelines Insights Breast Cancer, Version 1.2016.

These NCCN Guideline Insights highlight the important updates to the systemic therapy recommendations in the 2016 NCCN Guidelines for Breast Cancer. In the most recent version of these guidelines, the NCCN Breast Cancer Panel included a new section on the principles of preoperative systemic therapy. In addition, based on new evidence, the panel updated systemic therapy recommendations for women with hormone receptor-positive breast cancer in the adjuvant and metastatic disease settings and for patients with HER2-positive metastatic breast cancer. This report summarizes these recent updates and discusses the rationale behind them.

Breast Cancer Version 2.2015.

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This portion of the NCCN Guidelines discusses recommendations specific to the locoregional management of clinical stage I, II, and IIIA (T3N1M0) tumors.

Breast cancer version 3.2014.

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. The NCCN Guidelines specific to management of large clinical stage II and III tumors are discussed in this article. These guidelines are the work of the members of the NCCN Breast Cancer Panel. Expert medical clinical judgment is required to apply these guidelines in the context of an individual patient to provide optimal care. Although not stated at every decision point of the guidelines, patient participation in prospective clinical trials is the preferred option of treatment for all stages of breast cancer.

Cardiorespiratory Fitness in Patients With Early-Stage Breast Cancer and Radiation Therapy-Related Fatigue: A Prospective Pilot Study.

PURPOSE: Fatigue is among the most common but most poorly understood radiation therapy-associated toxicities. This prospective study sought to investigate whether cardiorespiratory fitness, an integrative measure of whole-body cardiopulmonary function, is associated with patient-reported fatigue in women with early-stage breast cancer undergoing radiation therapy. METHODS AND MATERIALS: Patients with stage Tis-T2N0M0 breast cancer and an Eastern Cooperative Oncology Group performance status of 0 to 1 undergoing breast radiation therapy performed a symptom-limited cardiopulmonary exercise test (CPET) on a motorized treadmill to assess cardiorespiratory fitness as measured by peak oxygen uptake (VO2peak). Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. Both assessments were performed during or immediately after radiation therapy completion. All patients were treated with an opposed tangent technique to a dose of 4240 cGy in 16 fractions with or without a lumpectomy bed boost. Patients receiving cytotoxic chemotherapy were excluded. Pearson correlation coefficients and univariate linear regression were used to assess associations amongVO2peak, fatigue, and patient characteristics. RESULTS: Twenty-eight patients (median age, 52 years; range, 31-71) completed a CPET and FACIT-Fatigue assessment. Median VO2peak was 25.1 mL O2.kg-1.min-1 (range, 16.7-41.7). The majority of patients (78.6%) displayed a VO2peak lower than their age-predicted VO2peak. Both age and body mass index were significantly associated with VO2peak levels. The median FACIT-Fatigue score was 41.5 (range, 10-52), with lower values indicating more fatigue. VO2peak was not significantly associated with FACIT-Fatigue score (P = .20). CONCLUSIONS: VO2peak was not a significant predictor of radiation therapy-related fatigue. Most patients with breast cancer had marked impairments in cardiorespiratory fitness as determined by VO2peak. Larger prospective studies are needed to further investigate this novel finding and evaluate the effects of interventions aimed at improving cardiorespiratory fitness and their ability to potentially prevent fatigue.