CA Breast

• Breast cancer is the most common malignancy in women worldwide (surpassed lung cancer in 2020 per GLOBOCAN data) ^[1][2].
• Lifetime risk in Western countries: approximately 1 in 8 women.
• Higher incidence in Caucasians compared to Asians and Africans, though the gap is narrowing as Asian countries undergo epidemiological transition (Westernised diet, later childbearing, decreased breastfeeding) ^[1].
• Male-to-female ratio ≈ 1:100 (some sources quote 1:2000 for overall population risk; the ratio of actual cases is ~1:100) ^[1][2].

The breast sits on the anterior chest wall overlying the pectoralis major (and partly serratus anterior), extending from the 2nd to 6th rib vertically and from the sternal edge to the mid-axillary line horizontally. The axillary tail of Spence extends superolaterally towards the axilla — important clinically because tumours here can be mistaken for axillary lymphadenopathy.

The breast is divided into four quadrants by a vertical and horizontal line through the nipple:

Why is the UOQ the most common site? Simply because it contains the most glandular tissue (the bulk of the breast parenchyma is concentrated superolaterally, including the axillary tail).

The TDLU consists of:

• Lobules (acini) — milk-producing glandular units
• Terminal ducts — drain each lobule
• Lactiferous ducts — converge towards the nipple (15–20 per breast), each draining a lobe
• Lactiferous sinuses — dilated segments just behind the nipple that store milk

Two cell layers line the ducts and lobules:

1. Inner luminal epithelial cells — secrete milk; give rise to most carcinomas
2. Outer myoepithelial cells — contractile cells that squeeze milk out; sit on the basement membrane

The key distinction between in-situ and invasive carcinoma is whether the malignant cells have breached through the myoepithelial cell layer and basement membrane.

Understanding lymphatic drainage is critical for staging and surgical planning:

Lateral tumours in the outer quadrant and centrally located lesions drain primarily to axillary lymph nodes. Upper and lower inner quadrant tumours drain to internal mammary lymph nodes. ^[1]

Sentinel lymph node (SLN): The first lymph node to which cancer cells are most likely to spread from a primary tumour, usually the node closest to the tumour. A negative SLN biopsy indicates that cancer has likely not spread to regional lymph nodes, and full axillary lymph node dissection (ALND) can be avoided — sparing the patient morbidity from lymphoedema ^[1].

• Arterial: Internal thoracic artery (perforating branches), lateral thoracic artery, thoraco-acromial artery, posterior intercostal arteries
• Venous: Corresponding veins — importantly, the vertebral venous plexus (Batson's plexus) provides a valve-less route for haematogenous metastasis to the spine and pelvis (explaining why bone is the most common site of distant metastasis)

The breast is an endocrine target organ:

• Oestrogen → stimulates ductal proliferation
• Progesterone → stimulates lobular/alveolar development
• Prolactin → stimulates milk production
• Oxytocin → stimulates myoepithelial contraction (milk let-down)

This hormonal dependence is fundamental to understanding both the aetiology (prolonged oestrogen exposure → increased risk) and treatment (anti-oestrogen therapy) of breast cancer.

Obesity risk depends on menopausal status ^[1]:

This is also why aromatase inhibitors (e.g., anastrozole, letrozole) are used as treatment in post-menopausal ER+ breast cancer — they block this peripheral conversion.

Physical inactivity also increases risk, likely through obesity-related and insulin resistance mechanisms ^[5][3].

Exposure to therapeutic ionising radiation — particularly chest/mediastinal radiation at a young age (e.g., mantle radiation for Hodgkin lymphoma) — significantly increases breast cancer risk. The younger the age at exposure, the higher the risk (developing breast tissue is more radiosensitive) ^[1][5].

A brief but important mention ^[2][6]:

1. Initiation: A genetic insult (inherited or acquired) causes a mutation in a proto-oncogene or tumour suppressor gene (e.g., TP53, PIK3CA, BRCA1/2 loss, HER2 amplification)
2. Promotion: Hormonal stimulation (especially oestrogen) drives proliferation of initiated cells, expanding the clone
3. Progression: Additional mutations accumulate (loss of cell cycle control, angiogenesis activation, evasion of apoptosis) → in-situ carcinoma
4. Invasion: Disruption of the basement membrane (loss of myoepithelial cell integrity, upregulation of matrix metalloproteinases) → invasive carcinoma
5. Metastasis: Invasion of lymphovascular spaces → lymphatic spread (regional LN) and haematogenous spread (distant organs)

Why is bone the most common site of distant metastasis? Breast cancer cells have tropism for the bone marrow microenvironment — they express CXCR4 (chemokine receptor) that binds to CXCL12 (SDF-1) produced by bone marrow stromal cells. Additionally, the vertebral venous plexus (Batson's plexus) provides a direct, valveless venous route from the breast/thoracic wall to the vertebral column.

This is the routine treatment-branching classification taught in the Cancer Block. It is based on hormone-receptor (HR) and HER2 status, not on PAM50. Here, HR+ means ER and/or PR positive ^[12]:

Professor Rina Hui emphasised using these four receptor-defined groups for the routine immunohistochemical classification of breast cancer ^[12].

Therefore, HER2-positive disease totals ~20%: about half HR+/HER2+ and half HR−/HER2+ ^[12].

Key receptors explained:

• ER (Oestrogen Receptor): A nuclear transcription factor. When oestrogen binds → activates gene transcription promoting cell proliferation. Tamoxifen is a selective oestrogen receptor modulator (SERM) that competitively blocks oestrogen binding.
• PR (Progesterone Receptor): Expression is oestrogen-driven; PR+ confirms a functioning ER pathway. PR+ tumours have even better prognosis among HR+ cancers.
• HER2 (Human Epidermal growth factor Receptor 2): A transmembrane tyrosine kinase receptor (ErbB2/neu). Amplification → constitutive activation of downstream RAS-MAPK and PI3K-Akt pathways → uncontrolled proliferation. Trastuzumab ("Herceptin") is a monoclonal antibody that binds the extracellular domain of HER2, blocking signalling and marking the cell for immune-mediated destruction (ADCC).

6.2.1 Driver and Resistance Alterations in Advanced Breast Cancer

The IHC subtype remains the first branching point, but metastatic disease now requires a second layer: which pathway is driving growth or resistance now? Re-biopsy and/or circulating tumour DNA (ctDNA) testing can reveal acquired alterations that were absent from the primary tumour ^[12][14].

True intrinsic molecular subtyping is based on gene-expression profiling. PAM50 analyses a 50-gene signature and assigns one of four intrinsic subtypes: luminal A, luminal B, HER2-enriched, or basal-like ^[12][17]. These names do not carry the “-like” suffix because they are molecular assay outputs.

PAM50 is not routinely performed for every breast cancer. A PAM50-based assay such as Prosigna may be used selectively to estimate recurrence risk in an eligible early HR+/HER2− population, but routine initial treatment branching still uses ER, PR and HER2 testing ^[17].

The TNM staging system classifies breast cancer based on:

T — Primary Tumour:

Edition and anatomy traps: LCIS is excluded from AJCC 8th staging. Tis (Paget) applies only without underlying DCIS or invasive carcinoma; otherwise stage the underlying lesion. Pectoralis muscle involvement alone is not T4a chest-wall invasion, and dermal invasion alone does not establish T4b. The nodal table below is clinical cN; postoperative pN also uses node counts and deposit sizes. NCI staging tables.

N — Regional Lymph Nodes (cN):

M — Distant Metastasis:

Anatomic stage examples: IA = T1N0M0; IB = T0–1N1miM0; IIA includes T2N0M0; IIB = T2N1M0 or T3N0M0. Do not copy the duplicated T2N0 entry in the faculty slide's IIB row (CMB59, p. 23).

Stage Grouping (broad groups; historical survival figures):

The AJCC 8th edition also introduced a Prognostic Stage that incorporates tumour grade, ER, PR, HER2 status, and genomic assays (e.g., Oncotype DX) — this can upstage or downstage patients relative to anatomic staging alone.

The CEWG uses a risk-stratified approach rather than blanket annual screening:

• Average risk: Women aged 44–69 with certain combinations of risk factors may consider mammography every 2 years after discussion of benefits and harms ^[9].
• Moderate risk: Mammography every 2 years may be considered ^[9].
• High risk: Annual mammography is generally advised (starting age depends on risk profile), with specialist follow-up ^[9].

• Routine monthly scheduled breast self-examination (BSE) is no longer recommended for average-risk women.
• Routine clinical breast examination (CBE) as a screening test in asymptomatic average-risk women is also not recommended.
• Preferred strategy: breast awareness (knowing normal baseline breast appearance/feel) and prompt medical review for any new change.

The 2024 ASCO-SSO guideline broadened eligibility beyond the older age-50/family-history rule ^[13]:

• Offer BRCA1/2 testing to all newly diagnosed patients aged ≤ 65 years.
• For patients aged > 65 years, offer testing when it could affect PARP-inhibitor eligibility or when there is TNBC, male breast cancer, suggestive personal/family history, Ashkenazi Jewish ancestry, or another founder-population risk.
• Offer testing to patients with recurrent disease who are candidates for PARP inhibition, regardless of family history, and to patients with a second primary breast cancer.
• Add high-penetrance genes such as PALB2, TP53, PTEN, STK11 and CDH1 when the phenotype or family history supports them. A variant of uncertain significance must not change management.

Test an affected relative first when feasible because this gives the most informative family result. However, "never test an unaffected person" is too absolute: an unaffected relative may appropriately undergo counselling and multigene testing when no affected relative is available and the pedigree remains strongly suggestive; a negative result may then be uninformative rather than reassuring.

The DDx depends heavily on age and characteristics of the lump ^[2]:

Why does age matter? Because the pre-test probability of malignancy changes dramatically with age. In a 20-year-old, a firm mobile lump is overwhelmingly likely to be a fibroadenoma. In a 55-year-old, the same lump mandates urgent triple assessment to exclude carcinoma. The background incidence of breast cancer rises exponentially with age (accumulation of somatic mutations + longer cumulative oestrogen exposure).

Now let us go through each differential in detail.

The most common benign tumour of the breast ^[1][2].

The most common benign disorder of the breast ^[1][8].

"Phyllodes" from Greek phyllon = leaf — refers to the characteristic leaf-like architecture on histology ^[1][2].

Nipple discharge is the second most common breast complaint. The critical question is: Is this physiological or pathological? ^[1][2]

History-taking for nipple discharge ^[2]:

• True nipple discharge? (from the nipple orifice, not skin)
• Unilateral or bilateral?
• Colour of discharge?
• Recent pregnancy/breastfeeding?
• Single duct or multiple ducts?
• Spontaneous or expressible?

DDx by colour ^[1][2]:

Malignancy is the underlying cause in 5–15% of cases of pathological nipple discharge, and the most common malignancy associated is DCIS ^[1].

Investigations for nipple discharge ^[2]:

• Triple assessment
• ± Nipple discharge cytology
• ± Ductogram / ductoscopy (to localise intraductal lesion before microdochectomy)

Why is breast cancer usually painless? Most breast cancers grow insidiously within the parenchyma without acutely stretching the breast capsule or involving pain-sensitive structures. Exceptions include inflammatory breast cancer (dermal lymphatic obstruction → rapid oedema → stretching → pain) and locally advanced cancers invading the chest wall or intercostal nerves.

Already covered in detail in the Classification section, but worth reiterating in the DDx context:

• DCIS: precursor to invasive ductal carcinoma (~1%/year). Mammographic microcalcifications. Manage with surgery ± RT ± endocrine therapy ^[2][3][7]
• LCIS: premalignant condition rather than true cancer ^[7][9] — a marker and precursor for bilateral invasive carcinoma (~1%/year). Usually an incidental finding. Classical LCIS → observation; pleomorphic LCIS → excision ^[2]

• Mass: onset, progression, cyclical changes
• Nipple: discharge (colour, unilateral/bilateral, single/multiple duct), retraction
• Skin: dimpling, peau d'orange, erythema, itchiness
• Constitutional symptoms: weight loss, bone pain, SOB (metastatic disease)
• Risk factor assessment: family history (BRCA — CA breast/ovary/prostate/pancreas), personal history (breast disease, chest RT), oestrogen exposure (menarche, menopause, parity, breastfeeding, COC/HRT)

• Positioning: 45° or sitting
• Exposure: Clavicle to upper abdomen, both breasts and axillae

Inspection:

• Size, symmetry, scars (3 Ss) ^[1]
• Skin changes: ulceration, dimpling, peau d'orange, erythema
• Nipple changes — the 5 Ds: Deviation, Discolouration, Dermatitis, Depression (retraction), Discharge ^[1]

Palpation of breast (start with normal side):

• Comment on: site, size, shape, border, surface, consistency, tenderness, mobility (to skin and to pectoralis muscle) ^[2]
• Include axillary tail

Palpation of axilla:

• Five groups: anterior, posterior, medial, lateral, apical ^[2]
• Comment on: number, site, size, consistency, tenderness, fixation ^[2]

Examination for metastatic disease ^[1]:

• Examine liver for hepatomegaly
• Examine bone for bone tenderness
• Examine lungs for effusion
• Neurological examination if brain metastasis suspected

Mammography (mammo = breast; -graphy = imaging) uses low-dose X-rays to produce images of breast tissue. It is the primary imaging modality for early detection of breast cancer ^[1][2].

When to use mammography:

• Only for females > 35 years — because younger women have denser breasts (more glandular tissue, less fat), reducing mammographic sensitivity ("finding a white tumour in a white background") ^[2]
• Can be performed in pregnant women with shielding ^[2]
• Always perform bilateral mammography when breast cancer is suspected (to detect synchronous contralateral breast cancer) ^[2][4]

Standard views ^[1][2]:

Why these two views? Together they provide two perpendicular projections that allow triangulation of a lesion's position within the breast. The CC view shows medial-lateral location; the MLO view shows superior-inferior location and uniquely captures the axillary tail (where many cancers occur).

How to present a mammogram ^[2] (important!):

1. Breast tissue appropriate for age (comment on density)
2. Views: CC and MLO
3. Location of mass — MLO: upper vs. lower half; CC: outer vs. inner quadrant
4. Features of malignancy

Mammographic Features — Benign vs. Malignant ^[1]:

Mass features:

• Spiculated (stellate) opacity with irregular borders → suggests malignancy ^[1][2]
• Architectural distortion (e.g., tent sign) → suggests malignancy ^[2]
• Smooth, well-circumscribed mass → suggests benign

Calcification features ^[1]:

Why do cancers cause microcalcifications? In DCIS especially, malignant cells within ducts undergo necrosis (particularly in the comedo subtype). The necrotic debris undergoes dystrophic calcification — calcium phosphate deposits in dead tissue. These tiny calcifications ( < 0.5 mm) are often the earliest mammographic sign of DCIS, visible before a palpable mass develops. This is why mammographic screening saves lives — it catches cancer at the pre-invasive stage.

Other malignant mammographic signs ^[2]:

• Pectoralis major involvement (only assessable on MLO view)
• Skin thickening / tethering
• Nipple involvement

Mammographic advantages ^[2]:

• Gold standard for breast cancer screening
• More sensitive for calcifications than USG
• Less operator-dependent than USG
• Used for annual screening

Mammographic limitations ^[1][2]:

• Can only depict a mass as abnormal or suspicious but cannot make definitive diagnosis ^[1]
• Obscuration of borders and extent of primary tumour by dense breast tissues (reduced sensitivity in young, dense breasts) ^[1]
• Limited localisation; difficult to see chest wall and axilla ^[2]
• Radiation exposure (small dose)

USG Features — Benign vs. Malignant ^[1]:

Mnemonic for suspicious USG features: "SHIT CME" ^[2] — same features used for thyroid nodule assessment: Solid, Hypoechoic, Irregular margins, Taller-than-wide, Calcification (micro), Microlobulation, Extra-thyroidal extension (in breast context = chest wall invasion).

USG assessment of axillary lymph nodes ^[2]:

• Suspicious LN feature: loss of fatty hilum (normal LN has a central hyperechoic fatty hilum; metastatic replacement obliterates this)

Roles of USG in characterising masses ^[1]:

• Simple cyst (anechoic, posterior acoustic enhancement, well-defined walls) → no further intervention due to low cancer risk
• Indeterminate cyst → aspiration under USG guidance
• Intracystic mass → aspiration or biopsy
• Solid mass → characterise as benign or malignant; absence of flow on Doppler does NOT exclude malignancy ^[1]

Indications for breast MRI ^[1][2]:

1. Equivocal results from mammogram or USG
2. Assessment of patients with breast implants (implants obscure tissue on mammogram)
3. Identify patients with clinically occult tumour presenting with positive axillary LN (unknown primary) ^[2]
4. Suspected multicentric or bilateral malignancy, especially invasive lobular carcinoma (ILC) (ILC is notorious for being mammographically and clinically occult due to its diffuse infiltrating pattern)
5. Determine extent of disease accurately, especially chest wall involvement (not fully included on mammographic projections)
6. Identify extent of residual disease after excision with positive margins
7. Pre-operative evaluation to improve surgical planning (help surgeons obtain clean margins)
8. Monitor results of neoadjuvant therapy (assess tumour shrinkage)
9. Screening in high-risk patients (genetic predisposition, e.g., BRCA carriers)
10. Paget's disease with negative mammogram ^[2]

MRI malignant features ^[1]:

• Spiculated or irregular margins
• Rim-like enhancement
• Heterogeneous internal enhancement
• Enhancing internal septa
• More rapid uptake of contrast is characteristic of malignant mass (nearly all invasive breast carcinomas enhance on gadolinium-contrast MRI; some benign lesions also enhance — hence low specificity) ^[1]

BI-RADS is a standardised reporting system applicable to both mammographic and ultrasound findings ^[1][10][11]. It translates subjective radiological impressions into a universally understood risk category that dictates the next management step:

Distant staging is risk- and symptom-directed. In an asymptomatic patient with low-risk early breast cancer, do not automatically order CXR, abdominal US, bone scan, PET-CT and tumour markers. For locally advanced/high-risk disease or suspected metastases, use an appropriate whole-body staging strategy (CT chest/abdomen/pelvis with bone imaging, or FDG PET-CT according to the clinical setting); avoid duplicating equivalent tests. Neurological symptoms require dedicated brain imaging, preferably contrast MRI.

CBC, renal/liver function and other treatment-specific bloods establish fitness and investigate suspected organ dysfunction. CA 15.3 and CEA do not diagnose breast cancer or screen asymptomatic survivors for recurrence; they may supplement assessment in established metastatic disease, alongside symptoms and imaging.

After curative treatment, follow-up centres on clinical assessment and mammography of remaining breast tissue. New symptoms trigger targeted investigations. NCI breast treatment PDQ, ASCO follow-up guideline.

If the lesion is cystic:

• Lump disappears after aspiration + clear fluid → no further investigation needed
• Residual thickening after aspiration OR blood-stained fluid → proceed to core biopsy

If the lesion is solid (FNAC result):

• Benign → observe or excise
• Atypical → core needle biopsy (need architecture)
• Malignant → treat as cancer

For non-palpable masses detected on screening:

When excisional biopsy is needed for a non-palpable lesion, the surgeon needs guidance to find it:

Every newly diagnosed invasive breast cancer should be tested for ER, PR and HER2 — for both therapeutic and prognostic purposes ^[1][11]:

Interpret the boundary correctly: ER staining in exactly 1% of nuclei is positive. ER-low disease has limited evidence for endocrine benefit and may behave differently from strongly ER-positive disease. For HER2, reflex-test IHC 2+ with ISH; uncommon dual-probe ISH groups require concurrent IHC review and, where specified, recounting. A ratio or copy number alone is not sufficient in every group. ASCO/CAP ER/PR guideline, HER2 algorithms, 2023.

HER2 biochemistry and clinical significance ^[1]:

• HER2 = Human Epidermal growth factor Receptor 2 (erbB2 gene)
• HER2 gene amplification is the primary mechanism for HER2 protein overexpression
• HER2 is a transmembrane receptor tyrosine kinase with no known direct ligand. It is a preferred dimerisation partner for other HER-family receptors; amplification/overexpression promotes signalling through pathways such as PI3K–AKT and RAS–MAPK. EGF binds EGFR/HER1, not HER2. This explains why trastuzumab, pertuzumab and HER2 TKIs interrupt different parts of the same pathway (faculty HER2 lecture, pp. 4, 7, 10–14).
• HER2 protein overexpression in breast cancer is associated with ^[1]:
  • Higher risk of recurrence
  • Higher mortality
  • Relative resistance to hormonal treatment
  • Less benefit from some forms of chemotherapy

IHC Scoring for HER2:

Sample pathology report interpretation ^[11]: A report stating "ER Negative, PR Negative, HER2 Score 0" with Ki67 60% describes a triple-negative breast cancer with high proliferative index. Triple-negative no longer means "no targeted treatment": metastatic therapy may still be selected by PD-L1, germline BRCA1/2 and ADC eligibility. HER2-low ADC eligibility requires the relevant IHC/ISH result; HER2-ultralow indications should not be extrapolated from HR-positive disease to TNBC. E-cadherin and myoepithelial markers such as p63 support interpretation with morphology and an appropriate panel; one stain alone does not prove ductal differentiation or invasion ^[11][12].

Read the report as a set of treatment decisions (faculty pathology lecture, pp. 2–24):

Use the published staging definitions for cell-count exceptions and detailed pN classification. NCI AJCC 8th tables.

At recurrence, biopsy an accessible metastatic site when clinically safe and useful. The metastatic clone may no longer match the primary tumour, so repeat ER, PR and HER2 assessment rather than automatically recycling the original subtype ^[12]. If tissue is difficult to obtain, plasma ctDNA can detect many somatic resistance alterations, but a negative plasma result may require tissue testing because low-shedding disease can produce a false negative.

There is no single "diagnostic criterion" — it is diagnosed by the combination of:

1. Clinical suspicion (hard, irregular, fixed mass ± skin/nipple changes)
2. Radiological suspicion (BI-RADS 4 or 5)
3. Histological confirmation on core needle biopsy showing malignant epithelial cells that have invaded through the basement membrane into the stroma

• Usually asymptomatic and non-palpable — detected by mammographic microcalcifications (linear branching or clustered pleomorphic) ^[1]
• Occasionally palpable (especially if large or high-grade)
• Histology: Malignant cells within TDLU with ductal predominance, WITHOUT invasion through basement membrane
• Grading: Low, Intermediate, High Grade ^[5][7]
  • High-grade (comedo) DCIS: central necrosis → dystrophic calcification → the characteristic mammographic microcalcifications
• Prognostic: Van Nuys Prognostic Index (considers size, margin width, grade/necrosis, age) ^[2] — guides treatment intensity

• NO symptoms or findings on physical examination AND mammography in most cases ^[1]
• Incidental finding on breast biopsy performed for another reason ^[1]
• Usually multifocal + multicentric + bilateral ^[1]
• Easily missed by mammography (rarely associated with microcalcifications) ^[1]
• E-cadherin NEGATIVE on IHC — this stain is used to clarify borderline cases between DCIS and LCIS (DCIS is E-cadherin positive; LCIS is negative due to loss of this cell-cell adhesion molecule) ^[1]
• Classical LCIS is both a non-obligate precursor and a marker of increased bilateral breast cancer risk. It is excluded from AJCC 8th TNM staging; this does not mean that it has no precursor role. Distinguish classical LCIS from pleomorphic/florid LCIS, which needs different management.

Diagnostic criteria (all must be met):

1. Rapid onset of breast erythema, oedema, peau d'orange or warm breast ± underlying palpable mass
2. Erythema occupying at least 1/3 of the breast
3. Duration of history no more than 6 months
4. Pathological confirmation of invasive carcinoma (skin punch biopsy showing tumour emboli in dermal lymphatics is characteristic but not required)

• Full-thickness wedge biopsy of the nipple showing Paget cells (malignant intraepithelial adenocarcinoma cells within the nipple epidermis)
• Mammography mandatory to look for associated mass and exclude synchronous cancers or widespread calcification ^[1]

BCT = Breast Conservation Surgery (BCS/Wide Local Excision/Lumpectomy) + Post-operative breast irradiation ^[1][12]

This is the preferred approach when feasible because it allows women with invasive breast cancer to preserve the breast with good cosmetic result ^[1] while achieving equivalent survival to mastectomy (proven in multiple randomised trials — NSABP B-06, Milan I).

Principles:

• Complete surgical removal of tumour with negative surgical margins ^[1]
• Negative margin defined as "no ink on tumour" ^[2] — meaning no tumour cells at the inked cut surface
  • Wider margin does NOT reduce recurrence or improve survival because adjuvant whole-breast RT eliminates subclinical foci ^[2]
  • Positive margin (ink on tumour) → > 2× increase in ipsilateral breast tumour recurrence (IBTR) ^[2]
• Adjuvant radiotherapy is COMPULSORY in BCT to eliminate subclinical foci of disease in the ipsilateral breast ^[1]

Selection criteria for BCS ^[1]:

• Tumour ≤ T2 ( ≤ 5 cm) without chest wall or skin involvement
• Appropriate tumour-to-breast ratio (cosmetically acceptable result after excision)
• Tumour is NOT multicentric
• Absence of distant metastasis
• Patient MUST agree to post-operative radiotherapy

Contraindications to BCS ^[1][2][12] (must know!):

Relative contraindication ^[12]:

• Multifocal disease (same quadrant) — may still be resectable in a single excision if feasible

Indications ^[2]:

• Contraindication to BCS (any of the above)
• Patient choice (desire to avoid post-operative radiation, further screening, or biopsy)
• Prophylaxis for patients with BRCA1/2 mutations or hereditary breast-ovarian syndrome ^[1]
• Similar efficacy to BCS (mastectomy does not improve survival over BCT — it simply removes more tissue) ^[2]

Types of Mastectomy:

Why did we move away from radical mastectomy? Halsted in the 1890s believed cancer spread in an orderly centrifugal fashion — remove more tissue, better cure. The Fisher hypothesis (1970s) revolutionised thinking: breast cancer is a systemic disease from early on, and local control (whether by mastectomy or BCT + RT) combined with systemic therapy determines survival, not the extent of surgery alone. This is why BCT achieves equivalent survival to mastectomy.

Practical surgical details ^[2]:

• Drains: Jackson-Pratt drain (closed suction) — placed through separate stab wounds inferolateral to main incision; ± 2nd drain at axilla if MRM
• Remove drains if output < 30 mL/day × 2 days ^[2]
• Locally advanced cases: may require removal of part of pectoralis muscle for margin; place clips in anticipation of subsequent RT; positive margin → adjuvant RT ^[2]

Methods:

• Autologous tissue flaps — e.g., TRAM (transverse rectus abdominis myocutaneous) flap, DIEP (deep inferior epigastric perforator) flap, latissimus dorsi flap
• Implant-based ^[13]:
  • One-stage: Permanent implant inserted at time of mastectomy
  • Two-stage: Tissue expander placed at mastectomy → gradually inflated → replaced with permanent implant ^[1]

The sentinel LN is the first draining LN group — the "gatekeeper" of the rest of the axillary LN ^[2][12].

Purpose: To find the first lymph node which drains the tumour ^[12]. If the sentinel node is negative, the remainder of the axilla is overwhelmingly likely to be negative too, and the patient is spared the morbidity of full axillary dissection.

Indications ^[1][2]:

• Early breast cancer with clinically negative nodes (for staging the axilla with less morbidity than ALND)
• Early stage (T1 or T2) cancer ^[1]
• DCIS with planned mastectomy (because SLNB cannot be done after mastectomy if occult invasive cancer is found — the lymphatic drainage is permanently altered) ^[1]
• DCIS with suspicious features (suspicion of harbouring synchronous invasive cancer: > 5 cm, palpable mass, high-grade/comedo) ^[1]

Contraindications ^[1]:

• Absolute:
  • Clinically positive nodes (should proceed directly to ALND)
  • Inflammatory breast cancer (T4d) (should be treated with ALND)
• Relative:
  • Tumour > 5 cm (T3)
  • Tumour with chest wall or skin involvement (T4a–T4c)
  • Previous breast or axillary procedures (disruption of lymphatic drainage → increased false-negative rate)

Technique ^[1][2][12]:

• Dual tracer injection to intradermal / subareolar / intratumoral region ^[2]:
  • Technetium-99m-labelled albumin — injected the day before surgery; detected intra-operatively by gamma probe ^[2]. Contraindicated in pregnancy ^[2].
  • Blue dye (methylene blue / isosulfan blue) — injected intra-operatively for direct visualisation of blue lymphatic channels and nodes ^[2]
• Injection should not be close to axilla (avoids interference) and lateral to previous scars (may block lymphatic drainage) ^[2]
• Remove maximum 3–4 sentinel LN ^[2] (HK practice: up to 4) ^[1]
• Frozen section of the LN to be done intraoperatively ^[12] — if positive, can proceed to ALND in the same operation

SLN Identification ^[1]:

• By blue dye: any blue node or any non-blue node with blue afferent lymphatic
• By radioactivity: remove the node with highest radioactive count (gamma probe); subsequent nodes removed by the "10% rule" — all nodes with > 10% of the ex vivo count of the hottest node should also be removed ^[1]

Results and management ^[2]:

Limitations of SLNB ^[2]:

• False-negative rate: 9.8% (NSABP B-32 trial)
• Only 75% of lymphatics drain to axilla (some drain to internal mammary chain)
• Skip metastases possible

New advancements ^[2]: ICG (indocyanine green fluorescence), SPIO (supra-paramagnetic iron oxide) — non-radioactive alternatives.

Indications ^[1][2]:

• Clinically positive nodes (by palpation / USG axilla)
• Positive sentinel LN (per criteria above — all patients receiving mastectomy without radiation with any macrometastasis; > 2 positive SLNs in BCT patients)
• Inflammatory breast cancer (T4d) ^[2]

Extent of resection ^[1][2]:

• Standard: Level I (lateral to pec minor) + Level II (deep to pec minor) — typically yields ≥ 10 lymph nodes ^[1]
• Level III dissection is NOT indicated unless grossly positive Level III nodes — increases morbidity significantly without improving survival; skip metastasis to Level III is rare ^[1][2]

Structures to preserve ^[1]:

• Thoracodorsal artery, vein, and nerve
• Long thoracic nerve

Complications of ALND ^[2] — remember the 4 nerves:

NO role of neoadjuvant radiotherapy in breast cancer treatment ^[1].

5.2.1 Adjuvant Radiotherapy

Rationale ^[1][2]:

• ↓ Locoregional recurrence rate
• ↓ Breast cancer mortality rate

Why is RT standard after BCS? The surgeon removes the macroscopic tumour, but microscopic disease (subclinical foci) may remain in the surrounding breast tissue. RT sterilises these residual foci, reducing local recurrence from ~30–40% (BCS alone) to ~5–10% (BCS + RT) — making BCT equivalent to mastectomy.

Indicated in ALL ER/PR+ cases unless contraindicated ^[2].

Rationale: Breast cancers that express ER depend on oestrogen for proliferation. Blocking this pathway → tumour growth arrest and apoptosis. This is the longest-duration adjuvant treatment — total treatment for 5–10 years ^[2].

In curative treatment, adjuvant endocrine therapy usually starts after chemotherapy. This sequencing reflects how the regimens were studied and avoids overlapping treatment burden; it should not be taught as a proven rule that tamoxifen simply "hides" every cancer cell from chemotherapy. In metastatic HR-positive disease, endocrine therapy is commonly combined with a targeted agent (especially a CDK4/6 inhibitor), whereas concurrent endocrine therapy plus cytotoxic chemotherapy is not routine outside a specifically studied regimen.

AIs are more effective than tamoxifen in post-menopausal women ^[2], but both remain valid options. The choice depends on side-effect profile and patient tolerance.

Bisphosphonates / Denosumab ^[1][2]:

• Osteoclast inhibitors — indicated for palliation in patients with bone metastasis ^[1]
• Bisphosphonates (e.g., pamidronic acid, zoledronic acid): reduce bone resorption → improve symptoms of bone pain, reduce skeletal-related events (SREs), improve QOL ^[1]
  • SREs = pathological fractures, spinal cord compression, hypercalcaemia of malignancy ^[1]
• Denosumab (RANKL monoclonal antibody) ^[1][2]: RANKL is the ligand that activates osteoclasts; blocking it → potent osteoclast inhibition
  • Slight benefit over bisphosphonates in preventing SREs and analgesic effect; counterbalanced by greater cost ^[1]
  • Advantage: quick monthly SC injection (not a prolonged IV infusion) ^[1]

1. Confirm and phenotype the recurrence: biopsy an accessible metastatic site if feasible; repeat ER, PR and exact HER2 IHC/ISH because receptor conversion occurs.
2. Stage the burden and urgency: identify brain metastases, impending fracture/cord compression, hypercalcaemia, malignant effusion and true visceral crisis.
3. Record prior exposure and endocrine sensitivity: de novo disease differs from relapse during adjuvant therapy or within 12 months of its completion.
4. Test actionable biology: PIK3CA, AKT1/PTEN, ESR1, germline BRCA1/2, PD-L1 CPS in TNBC, and broader NGS when a result could alter treatment ^[22][24][25].
5. Treat the patient as well as the scan: performance status, marrow reserve, cardiac/renal/hepatic function, menopausal status, fertility, symptoms, preferences and access all matter.