What are the recommended treatment options for a patient with breast cancer or at high risk of developing breast cancer, considering their individual risk factors, medical history, and preferences, as part of the Choosing Wisely (CW) trial for breast cancer management?

Choosing Wisely in Breast Cancer Management

Core Principle: Multidisciplinary Care in Specialized Centers

All breast cancer treatment must be delivered in specialized breast units by a multidisciplinary team including medical oncologists, breast surgeons, radiation oncologists, radiologists, pathologists, and breast nurses, with access to plastic surgeons, psychologists, physiotherapists, and geneticists when needed 1.

Patient-Centered Decision Making

• Information on diagnosis and treatment must be provided repeatedly, both verbally and in writing, in comprehensive and easily understandable form 1.
• Patients must be actively involved in all management decisions, with treatment strategy extensively discussed and accounting for patient preferences 1.
• A breast nurse or similarly trained practitioner should act as patient navigator to coordinate care 1.

Treatment Strategy Framework

Treatment decisions are based on three key domains 1, 2:

1. Tumor Characteristics

• Size and location of primary tumor
• Number of lesions and extent of lymph node involvement
• Pathology including biomarkers (ER, PR, HER2) and gene expression profiles 1, 2

2. Patient Factors

• Age and menopausal status
• General health status and comorbidities
• Fertility concerns in premenopausal women (must be discussed before any systemic treatment) 1

3. Patient Preferences

• Age alone should never be the sole determinant for withholding or recommending treatment 1

Surgical Management Principles

For Early Breast Cancer

• Breast-conserving surgery (BCS) is the preferred option for the majority of early breast cancer patients, using oncoplastic techniques when needed to maintain cosmetic outcomes 1, 2.
• No tumor at inked margin is required; >2 mm margin preferred for in situ disease 1.
• Sentinel lymph node biopsy (SLNB) is standard for axillary staging in clinically node-negative disease 1, 2, 3.
• Further axillary surgery after positive SLNB is not required for low disease burden (micrometastases or 1-2 positive nodes with postoperative tangential breast radiation) 1.
• Axillary radiation is a valid alternative to completion dissection regardless of breast surgery type 1, 2.

For Mastectomy Cases

• Breast reconstruction should be offered to all women requiring mastectomy 1, 3.
• Immediate reconstruction should be offered to most patients except those with inflammatory cancer 1, 3.

Surveillance and Follow-Up

After Curative Treatment

• History, symptom assessment, and physical examination every 3-6 months for first 3 years 1, 2.
• Every 6-12 months for years 4-5 1.
• Annually thereafter 1.

Imaging

• Annual mammography on intact breast(s) 1.
• Do not perform routine laboratory tests or imaging (except mammography) for recurrence detection in asymptomatic patients 1.
• Do not routinely screen with breast MRI unless patient meets high-risk criteria per ACS guidelines 1.

Risk Reduction Strategies

For High-Risk Women

• Risk assessment should include cancer family history 1.
• Offer genetic counseling if hereditary risk factors suspected (strong family history or age ≤60 with triple-negative breast cancer) 1.

Chemoprevention Options

• For high-risk women ≥35 years with 5-year predicted risk ≥1.67% (Gail Model), tamoxifen reduces breast cancer incidence 4.
• Tamoxifen is effective for metastatic breast cancer in women and men, particularly in ER-positive tumors 4.
• For DCIS after breast surgery and radiation, tamoxifen reduces risk of invasive breast cancer 4.
• Tamoxifen reduces contralateral breast cancer occurrence in patients receiving adjuvant therapy 4.

Surgical Risk Reduction

• For BRCA1/2 carriers, bilateral mastectomy reduces subsequent breast cancer incidence by 90-95% 3.
• Risk-reducing salpingo-oophorectomy should be considered per genetic/familial high-risk assessment guidelines 3.

Systemic Therapy Principles

Hormone Receptor-Positive Disease

• Endocrine therapy is preferred for metastatic disease unless rapid response warranted or endocrine resistance suspected 2.
• Patients must be counseled to adhere to adjuvant endocrine therapy 1.
• For metastatic HR-positive disease progressing on prior endocrine therapy, offer either endocrine therapy with/without targeted therapy or single-agent chemotherapy 1.
• For HR-positive HER2-negative metastatic disease with germline BRCA1/2 mutations no longer benefiting from endocrine therapy, offer oral PARP inhibitor (olaparib or talazoparib) in first-through third-line setting rather than chemotherapy 1.

HER2-Positive Disease

• HER2-directed therapy should be offered early to all HER2-positive metastatic patients, as single agent, combined with chemotherapy, or with endocrine therapy 2.

Triple-Negative Disease

• For metastatic triple-negative breast cancer after at least two prior therapies for metastatic disease, offer sacituzumab govitecan 1.
• For metastatic triple-negative breast cancer with germline BRCA1/2 mutations previously treated with chemotherapy, offer oral PARP inhibitor (olaparib or talazoparib) rather than chemotherapy 1.
• Platinum-based or nonplatinum-based regimens may be offered based on patient and provider assessment 1.

General Chemotherapy Principles

• Single-agent chemotherapy is preferred over combination therapy for HR-positive HER2-negative metastatic disease no longer benefiting from endocrine therapy 1.
• Combination regimens may be offered for symptomatic or immediately life-threatening disease requiring rapid response 1.
• Sequential monochemotherapy is preferred in metastatic disease without rapid progression or life-threatening visceral metastases 2.

Management of Treatment-Related Issues

Endocrine Therapy Considerations

• Hormone replacement therapy should not be prescribed after breast cancer treatment, except in specific cases 1, 5.
• For severe vaginal atrophy after failure of non-hormonal options, low-dose vaginal estrogen may be considered after thorough risk-benefit discussion 5.
• Vaginal DHEA (prasterone) is an alternative for women on aromatase inhibitors who haven't responded to non-hormonal options 5.
• Estradiol levels should remain in postmenopausal range for women on aromatase inhibitors 5.

Other Complications

• Counsel survivors on lymphedema prevention/reduction including weight loss for overweight/obese patients 1.
• Refer patients with lymphedema symptoms to knowledgeable therapist 1.
• Monitor lipid levels and provide cardiovascular monitoring as indicated 1.
• Assess for cognitive difficulties and refer for neurocognitive assessment if impaired 1.
• Assess body image concerns and offer adaptive devices or surgery when appropriate 1.

Common Pitfalls to Avoid

• Do not withhold treatment based solely on age 1.
• Do not perform routine SLNB in DCIS (only for specific indications) 1.
• Do not use concomitant chemo-hormonal therapy in metastatic breast cancer 1.
• Do not interpret tumor marker elevation in first 6 weeks of therapy as progression (may represent flare phenomenon) 1.
• Do not prescribe systemic estrogen replacement after breast cancer 1, 5.
• Effective non-hormonal contraception must be used by all premenopausal women taking tamoxifen and for approximately two months after discontinuing therapy 4.