What is the standard treatment approach for breast cancer?

Standard Treatment Approach for Breast Cancer

Breast cancer management requires a multidisciplinary team approach with treatment decisions based on disease stage, tumor biology (hormone receptor status, HER2 expression), and patient characteristics, following a sequential algorithm of surgery, radiation, and systemic therapy tailored to molecular subtype. 1

Multidisciplinary Team Structure

• All breast cancer patients should be managed by a specialized multidisciplinary team including medical oncologists, breast surgeons, radiation oncologists, breast radiologists, breast pathologists, and breast nurses to optimize outcomes 1
• Treatment decisions must incorporate tumor burden/location, biological markers, patient age, menopausal status, general health, and patient preferences 1

Diagnostic Workup and Staging

• Pathological diagnosis must follow WHO classification from surgical specimens obtained by breast-conserving surgery or modified radical mastectomy with axillary lymph node assessment 1, 2
• Each tumor requires individual assessment for histological type/grade, estrogen receptor (ER) and progesterone receptor (PR) status by immunohistochemistry, HER2 status, and proliferation markers (Ki67) 1, 2
• Routine staging includes complete blood count, routine chemistry (liver enzymes, alkaline phosphatase, calcium), contralateral mammography, clinical examination, and chest X-ray 1
• For high-risk disease, additional imaging with chest CT, abdominal ultrasound or CT, and bone scan is recommended 2
• FDG-PET-CT may replace traditional imaging for staging in high-risk patients when conventional methods are inconclusive 1

Treatment Algorithm by Stage

Early-Stage Breast Cancer (Stage I, IIa, IIb)

Surgical Management

• Breast-conserving surgery (BCS) is the preferred option for most early breast cancer patients, with oncoplastic techniques used to maintain cosmetic outcomes 1
• Sentinel lymph node biopsy (SLNB) is the standard for axillary staging in clinically node-negative disease, replacing full nodal clearance 1
• Further axillary surgery is not required following positive SLNB with low disease burden (micrometastases or 1-2 positive sentinel nodes) when treated with postoperative tangential breast radiotherapy 1
• When mastectomy is necessary, breast reconstruction should be offered to all women, with immediate reconstruction available to most patients except those with inflammatory cancer 1, 3

Radiation Therapy

• Radiation therapy is essential after breast-conserving surgery 1, 3
• Axillary radiation is a valid alternative in patients with positive sentinel lymph node biopsy, regardless of breast surgery type 1
• Post-mastectomy radiotherapy is recommended for patients with four or more positive axillary nodes or T3 tumors with positive nodes 2

Systemic Therapy

• Validated gene expression profiles should guide adjuvant chemotherapy decisions for appropriate patients 1
• For hormone receptor-positive disease, endocrine therapy is mandatory, with the combination of chemotherapy plus antiestrogen significantly improving progression-free and overall survival in postmenopausal women 3
• For HER2-positive disease, anti-HER2 therapy plus chemotherapy is required 2
• For triple-negative tumors, chemotherapy is the mainstay, with consideration of immunotherapy if PD-L1 positive 2
• For adjuvant treatment of node-positive breast cancer, paclitaxel 175 mg/m² intravenously over 3 hours every 3 weeks for 4 courses administered sequentially to doxorubicin-containing combination chemotherapy is recommended 4

Locally Advanced Breast Cancer (Stage IIIa, IIIb, IIIc)

• Primary (neoadjuvant) chemotherapy should be the initial treatment for locally advanced tumors, followed by surgery and/or radiation therapy, then adjuvant systemic therapy 5
• Most tumors respond with >50% decrease in size, and approximately 70% of patients experience down-staging through primary chemotherapy 5
• Breast conservation is possible for many patients with locally advanced disease after neoadjuvant therapy 5

Inflammatory Breast Cancer

• Combined modality therapy has dramatically changed outcomes, with 5-year survival rates of 35-60% and approximately one-third of patients surviving beyond 10 years without recurrence 5

Locally Recurrent Breast Cancer

• Isolated local-regional recurrence should be treated like a new primary with curative intent including adjuvant treatment modalities 3
• For hormone receptor-negative tumors, isolated local-regional recurrence requires treatment with curative intent including appropriate "secondary" adjuvant modalities 3

Metastatic Breast Cancer (Stage IV)

Treatment goals shift to improving quality of life and prolonging survival, as metastatic disease is treatable but not curable. 3, 6

Endocrine Therapy for Hormone Receptor-Positive Disease

• Endocrine therapy is the preferred first-line option for hormone receptor-positive metastatic disease unless rapid response is warranted or endocrine resistance is suspected 1
• Patients with evidence of endocrine resistance should be offered chemotherapy 3
• Concomitant chemohormonal therapy is not recommended 3

Available endocrine therapies include:

• Selective estrogen receptor modulators (SERMs): tamoxifen, toremifene 3
• Third-generation aromatase inhibitors: anastrozole, letrozole (non-steroidal); exemestane (steroidal) 3
• LHRH analogs: goserelin, leuprorelin, triptorelin, buserelin 3
• Estrogen receptor antagonist: fulvestrant 3
• Progestins: medroxyprogesterone acetate, megestrol acetate 3

Chemotherapy for Metastatic Disease

• Sequential monochemotherapy is preferred in metastatic breast cancer without rapid clinical progression or life-threatening visceral metastases 1
• After failure of initial chemotherapy or relapse within 6 months of adjuvant therapy, paclitaxel 175 mg/m² intravenously over 3 hours every 3 weeks is effective 4
• Commonly used single agents include anthracyclines, taxanes, capecitabine, vinorelbine, fluorouracil as continuous infusion, and gemcitabine 3
• There is no standard approach for second- or further-line treatment 3
• Continuing beyond third-line chemotherapy may be justified in patients with good performance status and response to previous chemotherapy 3
• High-dose chemotherapy shows no advantage in terms of overall or relapse-free survival 3

HER2-Directed Therapy

• HER2-directed therapy should be offered early to all HER2-positive metastatic patients, either as single agent, combined with chemotherapy, or with endocrine therapy 1
• Patients with HER2 overexpression (3+ immunohistochemistry or positive FISH/CISH) are candidates for trastuzumab with non-anthracycline chemotherapy 3
• Cardiac monitoring should be performed before and during trastuzumab therapy 3

Supportive Care

• Bisphosphonates are effective for hypercalcemia and palliate symptoms from lytic bone metastases 3
• Radiation therapy is integral for palliative control of painful bone metastases and central nervous system involvement 3, 5

Response Evaluation

• Response evaluation is recommended after 3 months of endocrine therapy and after 2-3 cycles of chemotherapy by clinical evaluation, symptom assessment, blood tests, and repeating initially abnormal radiologic examinations 3
• Serum tumor markers (CA 15-3) may be helpful for monitoring not easily measurable disease but should not be the only determinant for treatment decisions 3
• A phenomenon of tumor marker flare can occur in the first 6 weeks of effective therapy and must be considered when interpreting serial values 1

Follow-Up Care

• After curative treatment, follow-up should include history, symptom elicitation, and physical examination every 3-6 months for 3 years, then every 6-12 months thereafter 1
• Patients with metastatic disease should be seen frequently enough to provide optimal palliation of symptoms and maintain quality of life 3, 1

Special Populations and Considerations

Premenopausal Patients

• Fertility issues and preservation techniques should be discussed before initiating systemic treatment in younger premenopausal patients 1

Elderly Patients

• Age should not be the sole determinant for withholding or recommending treatment but should be considered along with other factors 1

AIDS-Related Kaposi's Sarcoma with Breast Cancer

• For patients with AIDS-related conditions requiring paclitaxel, reduce dexamethasone premedication to 10 mg PO, initiate treatment only if neutrophil count ≥1,000 cells/mm³, reduce dose by 20% for severe neutropenia, and initiate G-CSF as indicated 4

Hepatic Impairment

• Patients with hepatic impairment are at increased risk of toxicity, particularly grade III-IV myelosuppression, requiring dose adjustments based on transaminase and bilirubin levels 4

Common Pitfalls and Caveats

• Never administer paclitaxel to solid tumor patients until neutrophil count is ≥1,500 cells/mm³ and platelet count is ≥100,000 cells/mm³ 4
• Avoid concomitant chemohormonal therapy in metastatic breast cancer as it provides no benefit 3, 1
• Do not perform frozen section or primary axillary dissection for impalpable tumors without palpable macroscopic lesions 3
• Breast reconstruction should never interfere with administration of chemotherapy or radiotherapy 3
• Patients requiring dose reduction include those experiencing severe neutropenia (<500 cells/mm³ for ≥1 week) or severe peripheral neuropathy, requiring 20% dose reduction in subsequent courses 4