Breast Cancer: Treatment Options, Indications, and Contraindications

Definition / Overview

Breast cancer treatment is multimodal and requires careful integration of surgery, radiation, systemic therapy, and MDT decision-making. The choice of treatment is governed by tumour biology (receptor status, grade, HER2 amplification), disease stage (early, locally advanced, metastatic), patient fitness, and patient preference. The treating surgeon must be fluent in the indications and contraindications for each modality to lead informed consent discussions, contribute meaningfully to MDT recommendations, and manage operative and perioperative complexity.

Staging Framework

Clinical staging underpins all treatment decisions. The AJCC TNM system incorporates pathological and biological modifiers.

Surgical Options: Breast

Breast-Conserving Surgery (Lumpectomy / Wide Local Excision)

Definition: Excision of the primary tumour with a margin of surrounding normal tissue, preserving the remaining breast, followed mandatorily by adjuvant whole-breast radiotherapy.

Indications: - Early-stage disease (stage I-II) where tumour-to-breast volume ratio permits adequate resection with acceptable cosmesis - Patient preference for breast preservation - Unicentric disease (single lesion or closely grouped lesions resectable in one volume) - Tumour amenable to surgical localisation (wire, ROLL, SAVI SCOUT, radioactive seed) - Following successful neoadjuvant therapy with sufficient downstaging

Contraindications:

Margin Standard: - Invasive cancer: no tumour at the inked margin ("no ink on tumour") - DCIS: $\geq 2\,\text{mm}$ margin from inked surface - Failure to achieve these thresholds after re-excision mandates completion mastectomy

Oncoplastic Principles: - Volume displacement (local tissue rearrangement) or volume replacement (local/regional flap) techniques extend BCS eligibility - Requires symmetrisation of the contralateral breast in many cases - Oncological safety equivalent to standard BCS when margins are adequate

Mastectomy

Types: - Simple (total) mastectomy: Removal of all breast tissue including the nipple-areolar complex (NAC); sentinel node biopsy may be performed concurrently - Skin-sparing mastectomy (SSM): Preserves the skin envelope (NAC excised); facilitates immediate reconstruction - Nipple-sparing mastectomy (NSM): Preserves skin and NAC; requires sub-NAC margin biopsy to confirm no tumour involvement - Modified radical mastectomy (MRM): Simple mastectomy with level I-II axillary lymph node dissection; now rarely performed as a primary procedure given sentinel node techniques

Indications for Mastectomy: - Multicentric or diffuse disease - Tumour size precluding acceptable cosmesis with BCS - Patient preference - Contraindication to radiotherapy (prior breast irradiation, certain connective tissue disorders, pregnancy where radiation cannot be deferred) - Inability to achieve clear margins with BCS - Locally advanced/inflammatory breast cancer (post-neoadjuvant therapy) - BRCA1/2 carriers opting for risk reduction (therapeutic and/or contralateral prophylactic mastectomy) - DCIS where BCS is not feasible

Contraindications: - Stage IIIB-IV disease is not a contraindication per se, but mastectomy in stage IV (metastatic) disease is generally not performed with curative intent; local control indications must be carefully weighed - Severe medical comorbidity increasing operative mortality (relative) - Patient refusal (informed consent is paramount)

Contralateral Prophylactic Mastectomy (CPM)

Indications: - High-risk genetic mutation carriers (BRCA1/2, PALB2, TP53) with newly diagnosed unilateral breast cancer - Strong family history and documented elevated lifetime risk - Patient anxiety and informed preference following adequate counselling - Lobular carcinoma in situ (relative)

Contraindications: - Stage IIIB (inflammatory, T4), IIIC (N3), or stage IV disease - systemic oncological control takes absolute priority; no contralateral cancer risk outweighs the risk of disseminated primary disease - Severe medical comorbidity significantly increasing surgical morbidity/mortality - Unrealistic expectations without thorough counselling regarding residual risk (small amount of breast tissue remains) and reconstruction outcomes

Axillary Surgery

Sentinel Lymph Node Biopsy (SLNB)

Indications: - Clinically and radiologically node-negative (cN0) early breast cancer - Selected patients with small nodal burden after neoadjuvant therapy (targeted axillary dissection or SLNB ± clip-guided removal)

Contraindications: - Clinically/pathologically confirmed node-positive disease not undergoing neoadjuvant therapy (proceed to ALND) - Inflammatory breast cancer - Prior axillary surgery (relative - mapping may be unreliable) - Documented failure of sentinel node mapping after dual technique (blue dye + radiocolloid)

Axillary Lymph Node Dissection (ALND)

Indications: - Pathologically confirmed nodal metastasis not fulfilling Z0011 criteria for omission - Positive SLNB in patients undergoing mastectomy or where $\geq 3$ sentinel nodes contain macrometastases - Inflammatory breast cancer - Post-neoadjuvant setting with residual nodal disease beyond targeted thresholds - Sentinel node not identifiable

Z0011 Criteria (ALND may be omitted with positive SLN if ALL met): - $\leq 2$ positive sentinel nodes (macrometastasis) - BCS planned with whole-breast radiotherapy (tangential fields covering low axilla) - No matted nodes / extranodal extension on clinical examination - Not applicable to mastectomy patients (ALND or axillary radiotherapy required)

Systemic Therapy

Neoadjuvant Systemic Therapy

Indications: - HER2-positive or triple-negative breast cancer (TNBC) - neoadjuvant is the preferred strategy in operable disease to maximise pathological complete response (pCR) and prognostic information - Locally advanced disease (stage III) to achieve operability - Downstaging to permit BCS when primary surgery would require mastectomy - Inflammatory breast cancer (neoadjuvant therapy is always first-line) - Bulky nodal disease to permit sentinel node assessment post-treatment

Key Regimens: | Subtype | Backbone | |---|---| | HER2-positive | Anthracycline/taxane + dual HER2 blockade (trastuzumab + pertuzumab) | | TNBC | Anthracycline/taxane ± carboplatin; add pembrolizumab if PD-L1 positive (stage II/III) | | ER-positive/HER2-negative | Primary endocrine therapy (aromatase inhibitor) in post-menopausal patients seeking downstaging if chemotherapy is not indicated |

Contraindications to Neoadjuvant Chemotherapy: - Stage I, low-grade ER+/HER2− disease where chemotherapy would not be indicated adjuvantly (Oncotype DX/genomic testing guides decision) - Significant cardiac dysfunction (anthracycline-specific) - Patient refusal or inability to tolerate systemic treatment

Adjuvant Systemic Therapy

Chemotherapy: - Indicated for TNBC and HER2+ disease, high-grade ER+ tumours with high genomic risk (Oncotype Recurrence Score $\geq 26$ in pre-menopausal, $\geq 31$ in post-menopausal by trial data) - Regimens: anthracycline + cyclophosphamide → taxane (dose-dense or standard) - Capecitabine for residual TNBC after neoadjuvant (CREATE-X evidence)

Endocrine Therapy: - All ER and/or PR-positive tumours - Pre-menopausal: tamoxifen ± ovarian suppression (goserelin/leuprolide); high-risk pre-menopausal may benefit from aromatase inhibitor (AI) with ovarian suppression - Post-menopausal: AI (anastrozole, letrozole, exemestane) preferred over tamoxifen - Duration: 5-10 years depending on risk stratification - Contraindications to tamoxifen: active thromboembolic disease, pregnancy, concurrent potent CYP2D6 inhibitors (reduce active metabolite endoxifen); endometrial cancer history (relative) - Contraindications to AIs: pre-menopausal status without ovarian suppression (inadequate oestrogen suppression), severe osteoporosis without bone-protective therapy

HER2-Targeted Therapy: - Trastuzumab 12 months adjuvant for all HER2+ tumours $\geq T1b$ or node-positive - Extended adjuvant neratinib (tyrosine kinase inhibitor) for high-risk HER2+/ER+ patients - T-DM1 (ado-trastuzumab emtansine) for residual invasive disease post-neoadjuvant HER2+ therapy - Contraindication to trastuzumab: LVEF $< 50\%$ or significant symptomatic cardiac failure; requires baseline and serial echocardiographic monitoring

CDK4/6 Inhibitors (abemaciclib): - Adjuvant use in high-risk ER+/HER2− node-positive disease with Ki-67 ≥20% (monarchE trial) - Key toxicity: neutropenia, VTE, diarrhoea

Radiotherapy

Whole-Breast Irradiation (WBI)

Indications: - Mandatory adjuvant after all BCS for invasive cancer and DCIS - Standard: 40-42.5 Gy in 15-16 fractions (hypofractionation); equivalent oncological outcomes with shorter treatment duration

Contraindications: - Prior ipsilateral breast/chest-wall radiotherapy - Pregnancy (absolute during radiotherapy delivery; timing can be coordinated post-delivery) - Active inflammatory connective tissue disease involving the chest wall (scleroderma, active SLE - significant fibrosis risk) - Inability to achieve acceptable dosimetric plan due to anatomical constraints (rare)

Post-Mastectomy Radiotherapy (PMRT)

Indications: - $\geq 4$ positive axillary nodes - T3/T4 primary tumour - Positive or close deep margins after mastectomy - 1-3 positive nodes in high-risk patients (under ongoing trial evaluation; many centres treat routinely) - Inflammatory breast cancer (always)

Boost / Partial-Breast Irradiation

• Tumour-bed boost reduces local recurrence in high-risk patients (young age, grade 3, positive/close margins, lymphovascular invasion)
• Accelerated partial-breast irradiation (APBI) in selected low-risk patients ($\geq 50$ years, unifocal, ER+, node-negative, adequate margins)

Complications and Perioperative Considerations

Surgical Complications

Immediate Breast Reconstruction Considerations

• Implant-based: tissue expander or direct-to-implant; contraindicated when PMRT is planned (high capsular contracture and implant failure rates with radiotherapy)
• Autologous (TRAM, DIEP, latissimus dorsi): preferred when PMRT is required; better tolerates radiation; DIEP free-flap requires microvascular expertise
• BIA-ALCL (breast implant-associated anaplastic large cell lymphoma): rare but important late complication of textured implants - presents as delayed peri-implant effusion; treatment is total capsulectomy and implant removal

MDT Decision-Making and Evidence Synthesis

• All newly diagnosed breast cancers should be discussed at a multidisciplinary team meeting before definitive treatment
• Genomic profiling (Oncotype DX, MammaPrint) stratifies adjuvant chemotherapy need in ER+/HER2− early breast cancer and should be incorporated into treatment planning
• Neoadjuvant pCR (no residual invasive cancer in breast or nodes: $\text{ypT0/is ypN0}$) is a surrogate for improved event-free and overall survival in HER2+ and TNBC subtypes
• Fertility preservation: pre-menopausal patients should be referred to a reproductive endocrinologist prior to chemotherapy; GnRH agonist co-administration during chemotherapy reduces ovarian toxicity
• BRCA carriers with newly diagnosed breast cancer should have access to genetic counselling; bilateral risk-reducing salpingo-oophorectomy may also be discussed in the surgical planning MDT context

Perioperative Management

• DVT prophylaxis: LMWH (e.g., enoxaparin $40\,\text{mg}$ SC daily) initiated post-operatively; TED stockings and pneumatic compression intraoperatively; duration guided by oncological risk (extended prophylaxis for those on chemotherapy or with prolonged immobility)
• Antibiotic prophylaxis: single-dose cephazolin $2\,\text{g}$ IV at induction; extended to 24 hours for implant-based reconstruction
• Lymphoedema precautions: avoid cannulation, blood pressure measurement, and blood sampling in the ipsilateral arm post-ALND
• Cardiac surveillance: baseline LVEF before trastuzumab and every 3 months during treatment; hold if LVEF falls $> 10\%$ from baseline to $< 50\%$
• Bone health: patients on AIs require baseline DEXA scan; calcium and vitamin D supplementation; bisphosphonate (zoledronic acid) or denosumab if T-score $< -2.0$ or high fracture risk