Participants in this experimental (signle) arm will undergo an integrated breast cancer risk assessment combining the CanRisk model with polygenic risk score (PRS) testing. The intervention includes genetic counseling, blood collection for PRS analysis, and a comprehensive risk evaluation. Additionally, participants will complete a questionnaire to gather their feedback on the integrated PRS clinical pathway.

Standard genetic counseling followed by a blood draw (0.5 mL) for DNA extraction. The sample is processed using a high-throughput SNP genotyping platform, and the PRS, based on 313 SNPs, is calculated and integrated into the CanRisk model for refined breast cancer risk stratification.

Integrated PRS-Enhanced Breast Cancer Risk Assessment (CanRisk model)

Epirubicin (or Liposomal Doxorubicin)+Cyclophosphamide, intravenous infusion of 100 mg/m2. Epirubicin (or 35 mg/m2 liposomal doxorubicin)+600 mg/m2 cyclophosphamide+ 240 mg Toripalimab, starting from the first day of the week, for a total of 12 weeks.

Paclitaxel, administered intravenously at a dose of 260 mg/m2 every 3 weeks + 240 mg Toripalimab for a total of the following 12 weeks.

Epirubicin (or Liposomal Doxorubicin)+Cyclophosphamide, intravenous infusion of 100 mg/m2. Epirubicin (or 35 mg/m2 liposomal doxorubicin)+600 mg/m2 cyclophosphamide, starting from the first day of the week, for a total of 12 weeks. Paclitaxel, administered intravenously at a dose of 260 mg/m2 every 3 weeks for a total of 12 weeks. During neoadjuvant chemotherapy and postoperative adjuvant therapy, use of Toripalimab: intravenous infusion of 240 mg, once every 3 weeks, combined with preoperative neoadjuvant and postoperative adjuvant therapy for a total of 1 year.

Neoadjuvant Chemotherapy in Combination with Toripalimab

During neoadjuvant chemotherapy and postoperative adjuvant therapy, use of Toripalimab: intravenous infusion of 240 mg, once every 3 weeks, combined with preoperative neoadjuvant therapy and postoperative adjuvant therapy for a total of 1 year.

HR+ HER2 breast cancer

First Affiliated Hospital of Zhejiang University

Zhijun Dai

Yang Yu

Tong Liu

Ying Chen

Chaoyang Xu

Yili Wang

Wei Zhu

Hongtao Li

Xiaomin Yang

Huafeng Kang

Pengwei Lv

* Baseline breast MRI and research specimen collection prior to the start of treatment with standard of care anastrozole. All patients will have one 28-day cycle of anastrozole, followed by determination of breast cancer risk category by incorporating results from baseline Ki67, Oncotype DX RS, and molecular intrinsic subtype by PAM50.
* An additional blood draw for research purposes at Week 4 (no breast tumor biopsy at this time point) and continue to receive 5 additional 28-day cycles of anastrozole.
* After completion of \~6 months of neoadjuvant treatment, will undergo post-treatment breast MRI followed by standard of care surgery.

Ki67 scoring determination (standard of care) utilizing the Ki67 MIB-1 assay (clone 30-9) (VENTANA) will be performed at baseline, Week 4 (+/- 14 days - high-risk group only), and at time of surgery in accordance with the International Ki67 in Breast Cancer Working Group guidelines.

VENTANA MIB-1 Ki67 assay

Oncotype DX® Recurrence Score (RS) testing - assessing expression of 21 genes including 16 cancer-related genes and 5 reference genes - will be performed as standard of care in a central laboratory (Exact Sciences) on RNA extracted from formalin-fixed paraffin-embedded core-biopsy samples.

Oncotype DX® Recurrence Score

This PAM50-based Prosigna breast cancer gene signature assay for intrinsic molecular subtype determination will be performed on formalin-fixed, paraffin-embedded (FFPE) core-biopsy samples.

PAM50-based Prosigna breast cancer gene signature assay

Anastrozole

* Baseline breast MRI and research specimen collection prior to the start of treatment with standard of care anastrozole. All patients will have one 28-day cycle of anastrozole, followed by determination of breast cancer risk category by incorporating results from baseline Ki67, Oncotype DX RS, and molecular intrinsic subtype by PAM50.
* An additional blood draw and breast tumor tissue collection at Week 4 to assess Ki67. Patients with Week 4 Ki67 ≤10% (the high-risk endocrine-sensitive group) will continue to receive 5 additional 28-day cycles of anastrozole.
* After completion of \~6 months of neoadjuvant treatment, will undergo post-treatment breast MRI followed by standard of care surgery.

* Baseline breast MRI and research specimen collection prior to the start of treatment with standard of care anastrozole. All patients will have one 28-day cycle of anastrozole, followed by determination of breast cancer risk category by incorporating results from baseline Ki67, Oncotype DX RS, and molecular intrinsic subtype by PAM50.
* An additional blood draw and breast tumor tissue collection at Week 4 to assess Ki67. Patients with Week 4 Ki67 \>10% (the high-risk endocrine-resistant group) will receive escalated therapy with \~5-6 additional months of standard of care chemotherapy (combination anthracycline- and/or taxane-based at the discretion of their physician).
* After completion of \~6 months of neoadjuvant treatment, will undergo post-treatment breast MRI followed by standard of care surgery.

Combination anthracycline and/or taxane based treatment

Nusayba A Bagegni, M.D.

Cynthia X Ma, M.D., Ph.D.

Emily L Podany, M.D.

Katherine Weilbaecher, M.D.

Debbie L Bennett, M.D.

John Olson, M.D., Ph.D.

Katherine Glover-Collins, M.D., Ph.D.

Fouad Boulos, M.D.

Ian Hagemann, M.D., Ph.D.

Jingqin (Rosy) Luo, Ph.D.

Carolina Salvador, M.D.

The experimental group, determined by random selection, will include 68 women in menopause. These women will be asked to give their consent to participate in the study. After consent is obtained, a preliminary test will be conducted. Then, women in menopause will be educated on the symptoms and signs of breast cancer based on animation, self-breast examination, clinical breast examination, and mammography. The application will be conducted once a week. An interim test was conducted 14 days after the application, and a final test was conducted three months later.

The animation-based humorous application consists of four videos, each lasting 40-45 minutes, which separately explain the signs and symptoms of breast cancer, self-breast examination, clinical breast examination, and mammography through animation.

animation-based breast cancer education

No intervention was applied to the control group.

No intervention will be applied to the control group.

Control group (placebo)

Participants with metastatic breast cancer (MBC) receive the Promoting Resilience in Women with Breast Cancer (PRISM) intervention.

PRISM is a brief, skills-based intervention targeting 4 core resilience resources (stress management, goal setting, cognitive reframing, and meaning-making) followed by an optional family session. This adapted version of the PRISM intervention will be delivered1:1 by trained coaches who speak English or Spanish via HIPAA-compliant video conference.A single coach conducts the program with a single patient. Each session is 30-60 minutes, for a total of 2- 4 hours. Sessions are delivered every 1-2 weeks per patient's preference. To facilitate on-demand skills-practice between sessions, all participants have access to the PRISM app, available for iOS/Android, and thus available to the \>90% of U.S. adults who own a smartphone. Participants will be assisted to download the PRISM app to their device at the time of registration; however, coaches can also provide assistance with app access during intervention sessions.

Promoting Resilience in Women with Breast Cancer (PRISM)

UNC Lineberger Comprehensive Cancer Center

Gabrielle Rocque, MD, MSPH

Erin Laurie-Zehr, MA

Katie Reeder-Hayes, MD

The adaptive interventions include:

1. Non-specialist delivered Low intensity guided self-help (Khushi and Khatoon)
2. Moving on After Breast cancer Plus (Moving on ABC Plus)
3. Standard pharmacological intervention

This is a manualised intervention comprising of 8 chapters. This is being further co-adapted to contexualise this for breast cancer survivours. The original manual is focused on stories of two breast cancer survivors , Mrs Khushi, means happiness) and Khatoon, means woman in Urdu, with depression and anxiety, describing how they help themselves using CBT strategies.

Non-specialist delivered Low intensity guided self-help (Khushi and Khatoon)

This is a high intensity manualised intervention consisting of 12 sessions (60-90 minutes). This manual offers practical support and advice on life after breast cancer, managing difficulties, mindfulness, addressing fatigue, understanding the participant's model of illness, improving personal effectiveness and social relationships. The sessions also include therapist delivered psychoeducation using a CBT model of case formulation and goal setting: identification and formulation of predisposing, precipitating, perpetuating and protective factors of depression and/or anxiety, helping participants to identify core beliefs, where necessary, using downward arrow technique, identifying, and challenging unhealthy thinking patterns at the level of core beliefs using cognitive restructuring, and problem-solving techniques

Moving on After Breast Cancer (ABC) plus

Patients will begin 12 weeks of sertraline treatment initiated at a daily dose of 50 mg for the first 4 weeks. After that, flexible titation of sertraline will be permitted, by 50mg increment every 1 to 2 weeks, as clinically indicated and tolerated to a maximum daily dose of 200 mg

Standardised pharmacological treatment (antidepressants)

Participants in this arm will continue to follow their routine visits to healthcare facilities. They will be regularly monitored by trained research team and will be assessed at weeks 6,18,30, and 48. In addition to psychological assessment at each follow-up, this will include information leaflets based on a brief psychoeducational module to educate participants and families about the risks, symptoms, management, and referral support information for anxiety and depression

Enhanced Treatment As Usual (E-TAU)

Participants in this arm will continue to follow their routine visits to healthcare facilities. They will be regularly monitored by trained research team and will be assessed at weeks 6,18,30, and 48. In addition to psychological assessment at each follow-up, this will include information leaflets based on a brief psychoeducational module to educate participants about the risks, symptoms, management, and referral support information for anxiety and depression.

Pakistan Institute of Living and Learning

Tayyeba Kiran, PhD

Rabia Fahad, PhD Fellow

* Mastectomy with Immediate prosthetic breast reconstruction
* Adjuvant therapy by TomoTherapy (radiation therapy alone or preceded by chemotherapy).

Patients with invasive breast cancer will receive:

유방암 환자를 대상으로 초음파, 간소화 MRI, 전체 MRI의 진단 결과를 비교하는 시험입니다.

Women are classified and randomly assigned into MRI sequence groups(1st round screening/2nd round screening : AB (abbreviated)-MRI / FP (full protocol)-MRI application group and FP (full protocol)-MRI / AB (abbreviated)). MRI (either AB-MRI or FP-MRI) assigned as the 1st round screening (baseline), mammography, and ultrasound are performed on the same day. For the 2nd round screening one year after the 1st round screening, a different MRI (i.e., FP-MRI if AB-MRI was performed in the previous year, AB-MRI if FP-MRI was performed in the previous year), mammography, and ultrasound were performed on the same day as the 1st round screening.

Comparison of diagnostic results of abbreviated breast MRI and full protocol MRI for secondary breast cancer surveillance

Breast MRI for Breast Cancer Detection

여성은 MRI 시퀀스 그룹(1차 검진/2차 검진: AB(약어)-MRI/FP(전체 프로토콜)-MRI 적용 그룹 및 FP(전체 프로토콜)-MRI/AB(약어))으로 분류 및 무작위 배정되었습니다. 1차 검진(기준선)으로 배정된 MRI(AB-MRI 또는 FP-MRI), 유방촬영술, 초음파는 같은 날에 시행되었습니다. 1차 검진 1년 후 2차 검진의 경우, 다른 MRI(즉, 전년도에 AB-MRI를 시행한 경우 FP-MRI, 전년도에 FP-MRI를 시행한 경우 AB-MRI), 유방촬영술, 초음파를 1차 검진과 같은 날에 시행했습니다.

유방암 진단을 위한 유방 MRI

Yung Mi Park

Eun Sook Ko

Yun Woo Jang

유방암 진단을 위한 초음파와 유방 MRI 비교

Subject randomized to BCL surgical guidance to perform partial mastectomy

The BCL is a patient-specific, plastic, bra-like form which is placed on the breast to localize the tumor during surgery.

Breast Cancer Locator (BCL) guided partial mastectomy

Subject randomized to WL surgical guidance to perform partial mastectomy

Wire Localized (WL) partial mastectomy

Mother-daughter pairs will partake in an educational session at the baseline visit, which will cover topics on reading product labels, cleaning habit, and cooking methods for reducing environmental exposures. Educational materials will be adapted from the Environmental Protection Agency (EPA) and other accredited sources. Participants will also be introduced to free resources for consumer product safety information, such as the Detox Me phone application. Participants in the intervention arm will receive a 6-month supply of soap, lotion, deodorant, lip balm, a mop, cleaning cloths, and an air filter to take home with them. Mother-daughter pairs in both study arms will return for a second clinic visit 6 months after the pre-intervention visit for blood and urine sample collection, Optical Spectroscopy (OS) measurement, and questionnaire completion.

This study will focus the intervention on ways at the individual level to reduce sources of Polycyclic Aromatic Hydrocarbons (through cooking methods, exposure to cigarette smoking, indoor air filters) and also individual ways to reduce sources of other Endocrine Disrupting Chemicals. Mother-daughter pairs will partake in an educational session at the baseline visit, covering topics on reading labels, cleaning habits, and cooking methods for reducing exposures. Participants will also be introduced to free resources for consumer product safety information. The intervention arm will receive a 6-month supply of soap, lotion, deodorant, lip balm, a mop, cleaning cloths, and an air filter to take home with them. Pairs in both study arms will return for a second clinic visit 6 months after the pre-intervention visit for blood and urine sample collection, Optical Spectroscopy measurement, and questionnaire completion. The control arm will be offered the intervention products at this time.

Breast Cancer Risk Reduction Household Intervention

Mother-daughter pairs will partake in an educational session at the baseline visit, which will cover topics on reading product labels, cleaning habit, and cooking methods for reducing environmental exposures. Educational materials will be adapted from the Environmental Protection Agency (EPA) and other accredited sources. Participants will also be introduced to free resources for consumer product safety information, such as the Detox Me phone application. Mother-daughter pairs in both study arms will return for a second clinic visit 6 months after the pre-intervention visit for blood and urine sample collection, Optical Spectroscopy (OS) measurement, and questionnaire completion. Control arm participants will be offered the chemical-free products, cleaning supplies, and air filter at this time.

SMS reminders will be sent to individuals who received an invitation letter from Colorectal Cancer Screening Program and haven't participated within 6 weeks.

Individual randomization will be used. Individuals assigned to the experimental arm with a wrong phone number will get a reminder letter (protocol analysis).

SMS reminders to enhance colorectal cancer screening

Reminder letters will be sent to individuals who received an invitation letter from the Colorectal Cancer Screening Program and haven't participated within 6 weeks.

SMS reminders will be sent to individuals who picked the fecal immunochemical test at the pharmacy and haven't returned it within 14 days.

Individual randomization will be used. Individuals with a wrong phone number assigned to the experimental arm will not get any reminder (protocol analysis).

SMS reminders to return the fecal immunochemical test at the pharmacy in CRC screening:

Invitation by SMS will be sent to women who previously participated in the Breast Cancer Screening Program.

Individual randomization. Women assigned to the experimental arm and with a wrong phone number will get an invitation letter (protocol analysis).

Invitation by SMS to previous participants in breast cancer screening:

Intervention 1 and 2: both sexes. Intervention 3: only women.

The study staff will administer to eligible participants the pre-INT and post-INT surveys. The post-INT surveys will be administered approximately 8 months after delivering the INTs. The participants will receive the INT(s) immediately after completing the pre-INT surveys.

Adult men and women will receive age- and gender-specific INTs. Women age 45-75 years will receive the interventions for breast, colorectal, and cervical cancers screening. Men age 45-75 years will receive the intervention for colorectal cancer screening. Women age 21-49 years will receive the intervention for cervical cancer screening. The cognitive-behavioral INTs on age-gender specific cancers will range from 1-2 hours. The study team will utilize a digital flipchart that will cover each cancer's specific risk/protective factors, incidence, mortality, screening methods, and resources. The study team member delivering the INTs will function as a facilitator linking information with practical skills.

Aim 8 (INT, Pilot Test): Breast, Colorectal, and Cervical Cancer Screening Cognitive-Behavioral Interventions

Patients will receive standard of care (SOC) neoadjuvant chemotherapy and will be evaluated for enhanced clinical complete response (ecCR) after treatment. Participants who achieve an ecCR will be placed in the non-surgical arm. Participants will receive radiation therapy and routine and additional screening MRIs during follow up.

Participants will receive standard of care neoadjuvant chemotherapy

Neoadjuvant Chemotherapy

Radiotherapy simulation parameters will be at the discretion of the treating physician to account for the patient's body habitus, tumor bed location, and tolerability of the prone or supine positions, however, the recommended approach will be whole-breast RT (WBRT) in the prone position, for cT1-3 N0 patients who achieve ecCR. For cT1-2 N1 patients who achieve ecCR WBRT with nodal inclusion and lymph node boost will be performed in the supine position.

Radiation Therapy

Biopsy

Participants undergo blood and plasma collection

Biospecimen collection

Patients will receive standard of care (SOC) neoadjuvant chemotherapy and will be evaluated for enhanced clinical complete response (ecCR) after treatment. Participants who do not achieve an ecCR will be placed in the surgical arm. Participants will undergo a lumpectomy or mastectomy, receive radiation therapy, and routine follow-up.

Participants will undergo surgery to treat their breast cancer. Either a lumpectomy or a mastectomy will be performed.

Breast Cancer Surgery

Ohio State University Comprehensive Cancer Center

Sachin Jhawar, MD

Participants will undergo study procedures as outlined:

* Complete a baseline survey regarding exercise self-efficacy, physical activity level, quality of life, and fatigue
* Attend a 1-on-1 physical therapy evaluation and 4 group exercise sessions at MGH Waltham
* After completing the 4 exercise sessions, complete follow-up surveys including a program satisfaction survey
* At 1-month post-program, complete follow-up surveys and an individual, semi-structured interview with study staff to supply feedback about the program.
* At 3-months post-program, complete follow-up surveys

Individual physical therapy evaluation and 4 group-based exercise sessions led by a licensed physical therapist

Strength After Breast Cancer

These eligibility criteria are aligned with the criteria outlined by the developers of the Strength After Breast Cancer program. This program was developed for women after treatment for breast cancer.

통합 PRS 강화 유방암 위험 평가(CanRisk 모델)

토리팔리맙과 병용한 신보조 화학요법, HR+ HER2 유방암

VENTANA MIB-1 Ki67 분석, Oncotype DX® 재발 점수, PAM50 기반 Prosigna 유방암 유전자 시그니처 분석, 아나스트로졸, 안트라사이클린 및/또는 탁산 기반 치료의 조합

애니메이션 기반 유방암 교육, 대조군(위약)

유방암 여성의 회복력 증진(PRISM)

비전문가가 제공하는 저강도 가이드 자가 치료(Khushi 및 Khatoon), 유방암 이후의 전진(ABC) 플러스, 표준화된 약물 치료(항우울제), 평소와 같은 향상된 치료(E-TAU)

침습성 유방암 환자는 다음을 받게 됩니다.

유방암 진단을 위한 초음파와 유방 MRI 비교

유방암 위치 추적기(BCL) 유도 부분 유방 절제술, 와이어 국소화(WL) 부분 유방 절제술

유방암 위험 감소 가정 개입

대장암 검진 강화를 위한 SMS 알림, 대장암 검진 시 약국에서 대변 면역화학 검사를 반납하라는 SMS 알림, 유방암 검진에 참여한 이전 참가자에게 SMS로 초대:

목표 8(INT, 파일럿 테스트): 유방암, 대장암, 자궁경부암 검진을 위한 인지행동적 개입

신보조 항암화학요법, 방사선 치료, MRI, 유방암 수술, 생검, 생체 시료 채취

유방암 이후의 힘