Risk stratification of ER-positive breast cancer patients: A multi-institutional validation and outcome study of the Rochester Modified Magee algorithm (RoMMa) and prediction of an Oncotype DX® recurrence score <26.

The skyrocketing cost of health-care demands that we question when to use multigene assay testing in the planning of treatment for breast cancer patients. A previously published algorithmic model gave recommendations for which cases to send out for Oncotype DX® (ODX) testing. This study is a multi-institutional validation of that algorithmic model in 620 additional estrogen receptor positive breast cancer cases, with outcome data on 310 cases, named in this study as the Rochester Modified Magee algorithm (RoMMa). RoMMa correctly predicted 85% (140/164) and 100% (17/17) of cases to have a low- or high-risk ODX recurrence score, respectively, consistent with the original publication. Applying our own risk stratification criteria, in patients who received appropriate hormonal therapy, only one of the 45 (2.0%) patients classified as low risk by our original algorithm have been associated with a breast cancer recurrence over 5-10 years of follow-up. Eight of 116 (7.0%) patients classified as low risk by ODX have been associated with a breast cancer recurrence with up to 11 years of follow-up. In addition, 524 of 537 (98%) cases from our total population (n = 903) with an average modified Magee score ≤18 had an ODX recurrence score <26. Patients with an average modified Magee score ≤18 or >30 may not need to be sent out for ODX testing. By avoiding these cases sending out for ODX testing, the potential cost savings to the health-care system in 2018 are estimated to have been over $100,000,000.

The effects of high-dose calcitriol and individualized exercise on bone metabolism in breast cancer survivors on hormonal therapy: a phase II feasibility trial.

INTRODUCTION: Cancer treatment-induced bone loss (CTIBL) is a long-term side effect of breast cancer therapy. Both calcitriol and weight-bearing exercise improve bone metabolism for osteoporotic patients, but are unproven in a breast cancer population. We used a novel high-dose calcitriol regimen with an individualized exercise intervention to improve bone metabolism in breast cancer survivors. METHODS: We accrued 41 subjects to this open label, 2 × 2 factorial, randomized feasibility trial. Breast cancer survivors were randomized to receive the following: (1) calcitriol (45 micrograms/week), (2) individualized exercise with progressive walking and resistance training, (3) both, or (4) a daily multivitamin (control condition) for 12 weeks. Primary outcomes included changes in biomarkers of bone formation, bone resorption, and the bone remodeling index, a composite measure of bone formation and resorption. Safety measures included clinical and biochemical adverse events. A main effect analysis was used for these endpoints. RESULTS: Hypercalcemia was limited to three grade I cases with no grade ≥ 2 cases. Among exercisers, 100% engaged in the prescribed aerobic training and 44.4% engaged in the prescribed resistance training. Calcitriol significantly improved bone formation (Cohen's d = 0.64; p < 0.01), resulting in a non-significant increase in the bone remodeling index (Cohen's d = 0.21; p = 31). Exercise failed to improve any of the bone biomarkers. CONCLUSIONS: Both calcitriol and exercise were shown to be feasible and well tolerated. Calcitriol significantly improved bone formation, resulting in a net increase of bone metabolism. Compliance with the exercise intervention was sub-optimal, which may have led to a lack of effect of exercise on bone metabolism.

Oral curcumin for radiation dermatitis: a URCC NCORP study of 686 breast cancer patients.

PURPOSE: Despite advances in medical technology, radiation dermatitis occurs in 95% of patients receiving radiation therapy (RT) for cancer. Currently, there is no standard and effective treatment for the prevention or control of radiation dermatitis. The goal of the study was to determine the efficacy of oral curcumin, one of the biologically active components in turmeric, at reducing radiation dermatitis severity (RDS) at the end of RT, using the RDS scale, compared to placebo. METHODS: This was a multisite, randomized, double-blinded, placebo-controlled trial of 686 breast cancer patients. Patients took four 500-mg capsules of placebo or curcumin three times daily throughout their prescribed course of RT until 1 week post-RT. RESULTS: A total of 686 patients were included in the final analyses (87.5% white females, mean age = 58). Linear mixed-model analyses demonstrated that curcumin did not reduce radiation dermatitis severity at the end of RT compared to placebo (B (95% CI) = 0.044 (- 0.101, 0.188), p = 0.552). Fewer curcumin patients with RDS > 3.0 suggested a trend toward reduced severity (7.4 vs. 12.9%, p = 0.082). Patient-reported changes in pain, symptoms, and quality of life were not statistically significant between arms. CONCLUSIONS: Oral curcumin did not significantly reduce radiation dermatitis severity compared to placebo. The skin rating variation and broad eligibility criteria could not account for the undetectable therapeutic effect. An objective measure for radiation dermatitis severity and further exploration for an effective treatment for radiation dermatitis is warranted.

Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score.

Oncotype DX (Genomic Health, Redwood City, CA, USA, current list price $4,350.00) is a multigene quantitative reverse transcription-polymerase chain reaction-based assay that estimates the risk of distant recurrence and predicts chemotherapy benefit for patients with estrogen receptor (ER)-positive breast cancers. Studies have suggested that standard histologic variables can provide similar information. Klein and Dabbs et al have shown that Oncotype DX recurrence scores can be estimated by incorporating standard histologic variables into equations (Magee equations). Using a simple modification of the Magee equation, we predict the Oncotype DX recurrence score in an independent set of 283 cases. The Pearson correlation coefficient (r) for the Oncotype DX and average modified Magee recurrence scores was 0.6644 (n=283; P<0.0001). 100% of cases with an average modified Magee recurrence score>30 (n=8) or an average modified Magee recurrence score<9 (with an available Ki-67, n=5) would have been correctly predicted to have a high or low Oncotype DX recurrence score, respectively. 86% (38/44) of cases with an average modified Magee recurrence score≤12, and 89% (34/38) of low grade tumors (NS<6) with an ER and PR≥150, and a Ki-67<10%, would have been correctly predicted to have a low Oncotype DX recurrence score. Using an algorithmic approach to eliminate high and low risk cases, between 5% and 23% of cases would potentially not have been sent by our institution for Oncotype DX testing, creating a potential cost savings between $56,550.00 and $282,750.00. The modified Magee recurrence score along with histologic criteria may be a cost-effective alternative to the Oncotype DX in risk stratifying certain breast cancer patients. The information needed is already generated by many pathology laboratories during the initial assessment of primary breast cancer, and the equations are free.

Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients.

Radiation dermatitis occurs in approximately 95% of patients receiving radiotherapy (RT) for breast cancer. We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the ability of curcumin to reduce radiation dermatitis severity in 30 breast cancer patients. Eligible patients were adult females with noninflammatory breast cancer or carcinoma in situ prescribed RT without concurrent chemotherapy. Randomized patients took 2.0 grams of curcumin or placebo orally three times per day (i.e., 6.0 grams daily) throughout their course of RT. Weekly assessments included Radiation Dermatitis Severity (RDS) score, presence of moist desquamation, redness measurement, McGill Pain Questionnaire-Short Form and Symptom Inventory questionnaire. The 30 evaluable patients were primarily white (90%) and had a mean age of 58.1 years. Standard pooled variances t test showed that curcumin reduced RDS at end of treatment compared to placebo (mean RDS = 2.6 vs. 3.4; P = 0.008). Fisher's exact test revealed that fewer curcumin-treated patients had moist desquamation (28.6% vs. 87.5%; P = 0.002). No significant differences were observed between arms for demographics, compliance, radiation skin dose, redness, pain or symptoms. In conclusion, oral curcumin, 6.0 g daily during radiotherapy, reduced the severity of radiation dermatitis in breast cancer patients.

Polarity Therapy for cancer-related fatigue in patients with breast cancer receiving radiation therapy: a randomized controlled pilot study.

BACKGROUND: Cancer-related fatigue (CRF) is the most frequently reported side effect of cancer and its treatment. In previous research, Polarity Therapy (PT), an energy therapy, was shown to reduce CRF in patients receiving radiation. This study reports on a small randomized clinical trial designed to collect preliminary data on the efficacy of PT compared with an active control (massage) and passive control (standard care) for CRF among cancer patients receiving radiation therapy. METHODS: Forty-five women undergoing radiation therapy for breast cancer were randomized to 1 of 3 weekly treatment conditions. Patients received standard clinical care, 3 modified massages, or 3 PT treatments. CRF and health-related quality of life (HRQL) were assessed during baseline and the 3 intervention weeks. RESULTS: TResults show CRF ratings were reduced after PT. The effect sizes for PT versus modified massage and versus standard care were small when using the primary measure of CRF (Brief Fatigue Inventory) and large when using the secondary measure of CRF (Daily CRF Diaries).The effect size was medium when assessing the benefit of PT on maintaining HRQL compared with standard care with very little difference between the PT and modified massage conditions. Patients' feedback showed that both the modified massage and PT treatments were deemed useful by radiation patients. CONCLUSION: The present pilot randomized clinical trial supports previous experimental research showing that PT, a noninvasive and gentle energy therapy, may be effective in controlling CRF. Further confirmatory studies as well as investigations of the possible mechanisms of PT are warranted.

Irradiated autologous breast reconstructions: effects of patient factors and treatment variables.

BACKGROUND: Postmastectomy irradiation often negatively impacts breast reconstruction outcomes. Further investigation is necessary to recognize factors contributing to adverse results. The purpose of this study was to (1) accurately assess the impact of radiation on autologous breast reconstruction and (2) identify patient and treatment factors affecting reconstructive outcomes. METHODS: One hundred twenty-six patients were considered after postmastectomy breast reconstruction and irradiation. The records of 76 patients were studied after excluding for radiation therapy before reconstruction, complications before irradiation, implant reconstruction, mastectomy for recurrent disease, and history of cancer. Patient demographics and comorbidities, operative details, adjuvant therapy, and treatment outcomes were assessed. RESULTS: Seventy-six patients underwent autologous microsurgical breast reconstruction. Complications occurred in 53 patients (70 percent) 7.2 +/- 6 months after irradiation; 36 cases (47 percent) required reoperation for postirradiation effects. Parenchymal complications (fat necrosis or parenchymal fibrosis) were noted in 19.7 percent, skin complications (tissue envelope retraction or hypertrophic scarring) were recorded in 30.3 percent, and general dissatisfaction (physician or patient dissatisfaction) arose in 27.6 percent of patients. Parenchymal complications were associated with smoking (odds ratio, 9.3; p = 0.03), type II diabetes mellitus (odds ratio, 8.5; p = 0.02), and age (odds ratio, 1.1; p = 0.02). Neoadjuvant chemotherapy increased the development of complications (odds ratio, 4.4; p = 0.04), particularly skin changes (odds ratio, 2.4; p = 0.01). CONCLUSIONS: Patient-specific factors, including diabetes mellitus and smoking, increase the risk of postirradiation parenchymal changes, and neoadjuvant chemotherapy is associated with a greater than twofold increase in skin complications. Breast reconstruction followed by irradiation can be successful, but patients with specific risks should be aware of increased complication rates.

Angiosarcoma of the breast: a rare clinicopathological entity.

OBJECTIVES: Angiosarcoma is a rare subtype of sarcoma that usually arises after radiation therapy for primary breast cancer. Primary sarcomas of the breast are rare entities and account for less than 1% of all malignant breast neoplasms. We examine our institutional experience with angiosarcomas of the breast that were diagnosed and treated between 1996 and 2007. METHODS: To conduct a retrospective review, all female patients with a diagnosis of angiosarcoma of the breast were identified from our pathology database. Their hospital records were retrieved to gather information on treatment, tumor response, failure, and survival. RESULTS: A total of 8 patients were identified who had a histologically confirmed diagnosis of angiosarcoma of the breast. Median age was 70.3 years at diagnosis (range, 35.6-85.7 years). Seven (87%) patients had a history of prior radiation to the breast, whereas 1 (13%) had primary angiosarcoma. The median overall survival was 37.4 months (8.7-92.8 months) and relapse-free survival was 17.9 months (2.5-69.4 months). CONCLUSIONS: Even though angiosarcomas are rare neoplasms, they are increasingly recognized as the result of more breast-conserving therapy. High clinical suspicion and MRI may contribute to early diagnosis but a biopsy is always necessary to confirm it. These tumors tend to behave aggressively and require a multidisciplinary approach to improve the outcome.

Acupressure bands are effective in reducing radiation therapy-related nausea.

Previous studies have shown that acupressure bands can reduce chemotherapy-related nausea. Patients' expectations of efficacy account for part of this outcome. We conducted a three-arm randomized clinical trial to investigate the effectiveness of acupressure bands in controlling radiation therapy-induced nausea and to test whether an informational manipulation designed to increase expectation of efficacy would enhance the effectiveness of the acupressure bands. Patients who experienced nausea at prior treatments were randomized to either standard care (Arm 1, n=29) or standard care plus acupressure bands with either neutral (Arm 2, n=30) or positive (Arm 3, n=29) information regarding the efficacy of the bands. Patients reported nausea for two days prior to randomization (baseline) and for five days following using a seven-point semantic rating scale (1=not nauseated to 7=extremely nauseated). Patients in Arms 2 and 3 combined reported greater reduction in average nausea than patients in Arm 1 (P=0.01; mean(bands)=0.70, mean(no bands)=0.10). This equates to a 23.8% decrease in nausea in the band groups compared to a 4.8% decrease in the control group, a 19% difference. The informational manipulation failed to alter efficacy expectations and there was no statistically significant difference in nausea between patients in Arms 2 and 3. Acupressure bands are an effective, low-cost, nonintrusive, well-accepted, and safe adjunct to standard antiemetic medication. An attempt to boost the efficacy of the acupressure bands by providing positive information was not successful.