Bénaménil, France

A Vaccine (H2NVAC) Before Surgery for the Treatment of HER2-Expressing Ductal Carcinoma In Situ

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of multi-epitope HER2 peptide vaccine H2NVAC (H2NVAC) given for 4 treatments in patients with HER2-expressing ductal carcinoma in situ (DCIS) prior to surgery. II. To determine the dose level of H2NVAC with maximum systemic and intratumoral immunogenicity as measured by activated HER2-specific T lymphocytes or high-affinity antibodies. SECONDARY OBJECTIVES: I. To determine intratumoral immunogenicity of H2NVAC in patients with HER2-expressing DCIS. II. To assess the complete pathological response after 4 treatments of neoadjuvant H2NVAC. III. To assess the systemic immunogenicity of H2NVAC in patients with HER2-expressing DCIS. IV. To assess changes in HER2 expression in the DCIS after 4 treatments of neoadjuvant H2NVAC. V. To assess the distribution of the helper T cell response among T helper cell differentiation states. OUTLINE: This is a dose-escalation study of multi-epitope HER2 peptide vaccine H2NVAC. Prior to standard of care surgery, patients treated at dose levels 1 and 2 receive granulocyte macrophage-colony-stimulating factor (GM-CSF) admixed with multi-epitope HER2 peptide vaccine H2NVAC intradermally on day 1 of each cycle. Treatment repeats every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients treated at dose level 3 receive GM-CSF admixed with multi-epitope HER2 peptide vaccine H2NVAC intradermally on days 1, 4, 8, and 15 for 1 cycle. Patients also undergo echocardiography (ECHO) and collection of blood samples throughout the trial and may undergo biopsy on trial. After completion of study treatment, patients are followed up at 3, 6, and 12 months after surgery and optionally at 18 and 24 months after surgery.

Prospective Breast Cancer Biospecimen Collection

Topical Afimoxifene in Treating Patients With Breast Cancer Who Have Undergone Radiation Therapy on One Breast

PRIMARY OBJECTIVES: I. To identify the skin features that drive inter-individual variation in dermal drug permeation between individuals. SECONDARY OBJECTIVES: I. To relate breast tissue drug concentration to skin histology, skin vascularity, skin transporter proteins, and skin features measured using confocal reflectance microscopy. II. To assess the feasibility of transdermal drug delivery to the radiated breast. OUTLINE: Patients apply afimoxifene gel topically once daily (QD) to both breasts for 4 weeks and then undergo core needle biopsies of both breasts. Patients receive follow up phone call 21-35 days after biopsy.

Pre-operative SABR With and Without Caloric Restriction for Early Stage Breast Cancer

PRIMARY OBJECTIVE: I. To detect a decrease in cellularity of the tumor in participants undergoing caloric restriction during pre-operative SABR as compared to participants undergoing SABR alone. SECONDARY OBJECTIVES: I. Change in miR-21 as defined by baseline and post radiation levels. II. Investigate measurable changes of patient and tumor characteristics from the combination of SABR and caloric restriction (CR) versus SABR alone to inform future trials. III. To describe pathologic complete response (pCR) rates as defined by no residual carcinoma or no residual invasive carcinoma, but ductal carcinoma in situ (DCIS) may be present, in each arm as well as by subtype. IV. To assess response of each treatment arm using contrast-enhanced mammography (CEM) and correlate with pathologic response. V. To describe short term surgical outcomes including: sentinel lymph node (SLN) identification rate, positive margins requiring return to the operative room for re-excision, and post-operative complications (infection, delayed wound healing, seroma requiring aspiration). VI. To measure patient reported health-related outcomes and satisfaction with outcome. VII. To compare patient reported cosmesis to physician reported cosmesis scores, where cosmesis is rated as excellent, good, fair or poor. VIII. To compare pCR rates between women randomized to SABR alone to women randomized to SABR + CR who are at least 80% adherent to the CR intervention. IX. To compare pCR rates between women randomized to SABR alone who do not deviate by more than 10% from their baseline caloric intake to women randomized to SABR + CR who are at least 80% adherent to the CR intervention. EXPLORATORY OBJECTIVES: I. Tissue: To determine the downstream molecular effects of diet related to miR-21 such as FAS/FASL, PD-1, LAG3 and STAT3 expression. II. Microbiome: Compare baseline to post-SABR microbiome species separately for each trial arm. III. Serum: Determine if anti-tumor immunity has increased with increased CD8 and decreased Treg in tumor. Compare proteomic profiles. TERTIARY OBJECTIVE: I. To determine the ipsilateral breast recurrence rate, distant disease-free interval, recurrence free survival, and overall survival. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive standard dietary recommendations. Patients undergo SABR every other day for 5 fractions. Within 4-12 weeks of completion of SABR, patients undergo surgical resection with sentinel lymph node biopsy. ARM II: Beginning 1 week before the start of SABR, patients undergo a caloric restriction diet for 6-12 weeks (for the duration of radiation treatment, until post radiation follow-up appointment) consisting of reducing calorie intake by 25%. Patients undergo SABR every other day for 5 fractions. Within 4-12 weeks of completion of SABR, patients undergo surgical resection with sentinel lymph node biopsy. After completion of study intervention, patients are followed up at 3-6 weeks, and then 6 months after surgery.

Metformin and Nightly Fasting in Women With Early Breast Cancer

PRIMARY OBJECTIVES: I. To assess the safety of the experimental intervention based on the frequency of occurrence of a dose limiting toxicity (DLT) in the first 14 participants assigned to the experimental treatment arm. II. Evaluate the difference in post-treatment Ki67 labeling index (LI) in cancer adjacent ductal carcinoma in situ (DCIS) (in the presence of invasive breast cancer [IBC]), if present, or intraepithelial neoplasia (IEN) (defined as atypical ductal hyperplasia [ADH] or atypical lobular hyperplasia [ALH] or lobular carcinoma in situ [LCIS]) between the active treatment and the control group. SECONDARY OBJECTIVES: I. To explore the effect of intervention on the change of expression of PP2A-GSK3beta-MCL-1 axis in pre-post treatment cancer tissue levels. II. To measure the change in circulating biomarkers: Homeostatic model assessment (HOMA) index, highly sensitive C-reactive protein (CRP) (hsCRP), C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, Hb1Ac, lipid profile, adipokines (leptin and adiponectin). III. To correlate a customized next generation sequencing (NGS) mutational profile panel focused on estrogen receptor (ER) positive (+ve) with the response of Ki67. IV. To measure the difference of cell death by immunohistochemistry (IHC) for M30 in post- treatment cancer samples between arms. V. To measure the difference of phosphorylated (p)S6 by IHC in post- treatment cancer samples between arms. VI. To assess safety and toxicities according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0. VII. To correlate physiological distress, eating habits, tobacco and alcohol consumption with the response of Ki67 between arms. VIII. To compare the area under the curve (AUC) of glucose levels between arms and within the experimental arm according to different doses of metformin hydrochloride extended release (0 mg, 750 mg and 1500 mg). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients fast for >= 16 hours every night and use the continuous glucose monitoring system for 4-6 weeks. Patients also receive nutritional counseling sessions on days 0 and 10. Beginning week 2, patients also receive metformin hydrochloride extended release orally (PO) once daily (QD) until the day of surgery. Treatment continues for 4-6 weeks (until surgery) in the absence of disease progression or unacceptable toxicity. Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43). ARM II: Patients continue their usual dietary pattern and use the continuous glucose monitoring system for 4-6 weeks (until surgery). Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43). After completion of study intervention, patients are followed up at 30 days.

Neoadjuvant Breast Cancer Time Restricted Eating

Primary objective: 1. To evaluate the proportion of patients that can adhere to Time Restricted Eating (TRE) in patients with HER2 negative breast cancer who receive neoadjuvant chemotherapy (NCT) for a new diagnosis of stage I-III breast cancer. Secondary objectives: 1. To evaluate the pathologic complete response (pCR) rate of TRE in patients with HER2 negative breast cancer who receive NCT for a new diagnosis of stage I-III breast cancer 2. To evaluate the effect of TRE on weight management (prevention of weight gain), measured by BMI and waist circumference, in patients who are undergoing NCT. 3. To evaluate the percent of patients who develop CTCAE version 5.0 grade 3 or 4 toxicities 4. To evaluate the differences in the pCR rate among breast cancer patients within different race/ethnic groups, African American vs. Non-Hispanic White (AA vs NHW), and based on baseline social determinants of health when undergoing NCT 5. To evaluate if study intervention acceptability, adherence, and engagement differ by race (AA vs NHW) and based on baseline social determinants of health. 6. To evaluate if percent of patients with CTCAE version 5.0 grade 3 or 4 toxicities differ by race (AA vs NHW) and based on baseline social determinants of health. Exploratory objectives: 1. To monitor changes in the following inflammatory markers in patients undergoing neoadjuvant chemotherapy with TRE: fasting glucose, hemoglobin A1c, insulin, C-peptide, CRP, leptin, adiponectin,IGF-1, IL-6, TNF-α, and free fatty acids and lipids 2. To measure changes in markers involved in metabolic and lipogenic signaling pathways, immune modulation, and autophagy in adipocytes, tumor cells, and surrounding immune cells by Reverse-Phase Protein microarrays (RPPA) analysis. For this analysis we will use on tissue from baseline diagnostic tissue biopsies and post TRE plus neoadjuvant chemotherapy surgical tissue resection, when available

Surgical Excision vs Neoadjuvant Radiotherapy+Delayed Surgical Excision of Ductal Carcinoma

There will be measurable histopathological treatment effects identified in Arm 2 cases receiving pre-operative radiation. Results found are expected to assist in designing a more definitive study. Compare pathological findings in individuals with ductal carcinoma in situ (DCIS) who have surgical excision versus neoadjuvant radiotherapy followed by delayed surgical excision. It is noted that "phase 2" is formally associated with drug studies. Nonetheless, it is however part of the time of this study.

Decision Making Tool in Supporting Decision Making in Contralateral Prophylactic Mastectomy in Patients With Newly Diagnosed Breast Cancer

PRIMARY OBJECTIVES: I. An online decision support tool will be field tested that provides patients facing a decision about contralateral prophylactic breast cancer (CPM) with evidence-based information about the expected incidence of contralateral breast cancer and the life expectancy benefit of CPM. The tool will be designed for use in clinical settings and viewed jointly by the patient and physician as part of a shared decision making process around CPM. OUTLINE: Patients use decision making tool during consultation with breast cancer surgeon and complete questionnaires before and after consultation.

Women Informed to Screen Depending on Measures of Risk (Wisdom Study)

For almost 30 years, annual mammograms for women over 40 have been a cornerstone of the US strategy to reduce mortality from breast cancer. A number of advances in the understanding of breast cancer biology, and screening in general, have led to calls to revise and improve national screening strategies (Esserman et al., 2014). In 2009, the US Preventive Services Task Force (USPSTF) introduced changes to screening guidelines, recommending that annual mammograms for all women 40-75 be replaced by biennial screening for women ages 50-75, and that screening in the 40's should be individualized by taking patient context into account, including the patient's values regarding specific benefits and harms. Despite being based on a thorough review of the scientific literature, these recommendations continue to spark debate and scientific opinion on the effectiveness of annual screening is greatly divided. On one hand the radiology and obstetrics/gynecology community argues that annual mammograms starting at 40 reduce the rate of interval cancers. On the other hand, primary care physicians and other specialists believe that annual screening results in more false-positives and unnecessary treatment and that a more targeted approach could result in fewer false-positives and less over-diagnosis without increasing the number of interval cancers. In fact it has been estimated that half of women will receive a false-positive recall over 10 years of annual screening and that as many as 20% of all breast cancers might be overdiagnosed. Since 2009 this debate has intensified, paralyzing the system and thwarting any efforts to change or improve screening. The end result is that women are frustrated and confused, and some have stopped screening altogether. Despite a vastly improved understanding of breast cancer risk, the only criteria used to establish a woman's screening recommendations is her age (and BRCA status if known), but there are risk models available that incorporate personal and family history of breast disease, endocrine exposures and breast density to assess breast cancer risk (Constantino, et al., 1999; Parmigiani, et al., 1998; Tyrer, et al., 2004; Claus, et al., 2001; Ozanne, et al., 2003). Most recently certain genetic mutations and common genetic variants (single nucleotide polymorphisms or SNPs) have been confirmed predictors as well (Darabi, et al., 2012). Therefore, advances in this understanding of breast cancer biology, risk assessment, and imaging have enabled the creation of better tools and sufficient knowledge to replace the one-size-fits-all approach to screening and to implement a new, personalized model; one that provides recommendations on when to start, when to stop, and how often to screen that depend upon well characterized measures of risk. The investigators propose to test a transformational evidence-based approach to breast screening that educates women about their actual risk, and tailors screening recommendations to them as individuals. Within the Athena Breast Health Network, the study will compare comprehensive, patient-centered risk-based screening to annual screening for women starting at age 40. The comprehensive risk assessment is based on a widely accepted risk model, the Breast Cancer Surveillance Consortium model, that includes endocrine exposures, family history and breast density, with additional genomic risk factors that include rare and uncommon major breast cancer susceptibility alleles as well as more common and recently validated single nucleotide polymorphisms (SNPs) that can, cumulatively, contribute significantly to a woman's individual risk. The study's personalized approach will recommend an age to start and stop screening as well as a frequency based upon individual risk. Women of highest risk will receive greater surveillance than those of lowest risk where the lower bound is the USPSTF recommended guidelines. In this manner, the study will focus the most effort on those most likely to develop the disease. In close collaboration with patient advocates, the study has been designed as a 5-year, preference-tolerant, 65,000 patient, randomized controlled trial of risk-based versus annual screening. Individuals uncomfortable with the potential to be assigned to a particular arm in the randomized cohort can participate in the self-assigned observational cohort, an example of the pragmatic approach taken. Total accrual is anticipated to be 100,000 women across both cohorts. A broad group of stakeholders have participated in crafting this approach, including advocates, payers, the entire range of medical specialists and primary care providers and researchers involved with breast cancer screening across the entire Athena Network, technology partners, the Office of the President at the University of California, and policy-making organizations. The study hypothesizes that risk-based screening will be an improvement over annual screening because it will be as safe, less morbid, enable more cancer prevention, less stressful and more readily accepted by women as a result of an improved understanding of their personal risk. The Athena Breast Health Network was established across the 5 University of California medical centers to develop a new, harmonized approach to breast cancer prevention, screening and treatment. Athena is among the few centers in North America to use technology to integrate risk assessment into breast screening. The investigators have developed a cadre of "breast health specialists" who provide women with counseling and support around risk and prevention. There are currently 100,000 registered Athena participants, with 30,000 new patients per year and growing with the addition of Sanford Health, one of the largest rural health networks in the country. The primary research mission of Athena is to address issues requiring a population-based approach and translate solutions to clinical practice. Athena is uniquely positioned to address the screening controversy and provide women with renewed confidence in decisions about their breast health. Risk-based screening for breast cancer is exactly the advanced, evidence-based approach to medicine described in the NIH and FDA's "Path to Personalized Medicine". If these hypotheses prove to be correct, this study will be able to establish a clear justification for its use, and provide a framework for widespread implementation that will benefit women across the country.

Intra-operative Radiotherapy For Women With Ductal Carcinoma in Situ Breast Cancer

Giving radiation during surgery followed by external-beam radiation to the entire breast may kill more tumor cells.The clinical trial is conducting to find out the effectiveness of radiation therapy during surgery in treating women who have undergone breast-conversing surgery for low grade ductal carcinoma in situ breast cancer.