The COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS)

Introduction Ductal carcinoma in situ (DCIS) is a noninvasive non-obligate precursor of invasive breast cancer. With guideline concordant care (GCC), DCIS outcomes are at least as favourable as some other early stage cancer types such as prostate cancer, for which active surveillance (AS) is a standard of care option. However, AS has not yet been tested in relation to DCIS. The goal of the COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial for low-risk DCIS is to gather evidence to help future patients consider the range of treatment choices for low-risk DCIS, from standard therapies to AS. The trial will determine whether there may be some women who do not substantially benefit from current GCC and who could thus be safely managed with AS. This protocol is version 5 (11 July 2018). Any future protocol amendments will be submitted to Quorum Centralised Institutional Review Board/local institutional review boards for approval via the sponsor of the study (Alliance Foundation Trials). Methods and analysis COMET is a phase III, randomised controlled clinical trial for patients with low-risk DCIS. The primary outcome is ipsilateral invasive breast cancer rate in women undergoing GCC compared with AS. Secondary objectives will be to compare surgical, oncological and patient-reported outcomes. Patients randomised to the GCC group will undergo surgery as well as radiotherapy when appropriate; those in the AS group will be monitored closely with surgery only on identification of invasive breast cancer. Patients in both the GCC and AS groups will have the option of endocrine therapy. The total planned accrual goal is 1200 patients. Ethics and dissemination The COMET trial will be subject to biannual formal review at the Alliance Foundation Data Safety Monitoring Board meetings. Interim analyses for futility/safety will be completed annually, with reporting following Consolidated Standards of Reporting Trials (CONSORT) guidelines for noninferiority trials

Trends in complementary/alternative medicine use by breast cancer survivors: Comparing survey data from 1998 and 2005

BACKGROUND: Use of complementary and alternative medicine (CAM) by women with breast cancer is often said to be increasing, yet few data exist to confirm this commonly held belief. The purpose of this paper is to compare overall patterns of CAM use, as well as use of specific products and therapies at two different points in time (1998 vs 2005) by women diagnosed with breast cancer. METHODS: Surveys were mailed to women randomly selected from the Ontario Cancer Registry (Canada) in the spring of 1998 (n = 557) and again in the spring of 2005(n = 877). RESULTS: The response rates were 76.3% in 1998 and 63% in 2005. In 1998, 66.7% of women reported using either a CAM product/therapy or seeing a CAM therapist at some time in their lives as compared with 81.9% in 2005 (p = 0.0002). Increases were seen in both use of CAM products/therapies (62% in 1998 vs. 70.6% in 2005) and visits to CAM practitioners (39.4% of respondents in 1998 vs 57.4% of respondents in 2005). Women in 2005 reported that 41% used CAM for treating their breast cancer. The most commonly used products and practitioners for treating breast cancer as reported in 2005 were green tea, vitamin E, flaxseed, vitamin C, massage therapists and dietitians/nutritionists. CONCLUSION: CAM use (both self-medication with products and visits to CAM practitioners) increased significantly from 1998 to 2005. Now that more than 80% of all women with breast cancer report using CAM (41% in a specific attempt to management their breast cancer), CAM use can no longer be regarded as an "alternative" or unusual approach to managing breast cancer

The impact of patient characteristics and lifestyle factors on the risk of an ipsilateral event after a primary DCIS: a systematic review

ObjectiveThe ma­jor­ity of ‘low-risk’ (grade I/​II) Duc­tal Car­ci­noma In Situ (DCIS) may not progress to in­va­sive breast can­cer dur­ing a wom­en's life­time. There­fore, the safety of ac­tive sur­veil­lance ver­sus stan­dard sur­gi­cal treat­ment for DCIS is prospec­tively be­ing eval­u­ated in clin­i­cal tri­als. If proven safe and se­lec­tively im­ple­mented in clin­i­cal prac­tice, a sig­nif­i­cant group of women with low-risk DCIS may forego surgery and ra­dio­ther­apy in the fu­ture. Iden­ti­fi­ca­tion of mod­i­fi­able and non-mod­i­fi­able risk fac­tors as­so­ci­ated with prog­no­sis af­ter a pri­mary DCIS would also en­hance our care of women with low-risk DCIS.MethodsTo iden­tify mod­i­fi­able and non-mod­i­fi­able risk fac­tors for sub­se­quent breast events af­ter DCIS, we per­formed a sys­tem­atic lit­er­a­ture search in PUBMED, EM­BASE and Sco­pus.ResultsSix out of the 3870 ar­ti­cles re­trieved were in­cluded for fi­nal data ex­trac­tion. These six stud­ies in­cluded a to­tal of 4950 pa­tients with pri­mary DCIS and 640 recorded sub­se­quent breast events. There was mod­er­ate ev­i­dence for an as­so­ci­a­tion of a fam­ily his­tory of breast can­cer, pre­menopausal sta­tus, high BMI, and high breast den­sity with a sub­se­quent breast can­cer or fur­ther DCIS.ConclusionThere is a lim­ited num­ber of re­cent stud­ies pub­lished on the im­pact of mod­i­fi­able and non-mod­i­fi­able risk fac­tors on sub­se­quent events af­ter DCIS. The avail­able ev­i­dence is in­suf­fi­cient to iden­tify po­ten­tial tar­gets for risk re­duc­tion strate­gies, re­flect­ing the rel­a­tively small num­bers and the lack of long-term fol­low-up in DCIS, a low-event con­di­tion.</p

Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)

One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab

Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)

Purpose: One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 x 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab. Patients and Methods: Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m2 once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. Results: Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P � .0018) or bevacizumab (59% v 48%; P =.0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated. Conclusion: In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent

Microcalcification crystallography as a potential marker of DCIS recurrence

Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation. [Abstract copyright: © 2023. The Author(s).