Special Surgery 32. Breast Cancer: Diagnostics and Treatment

I. Definition, Epidemiology, Risk Factors and Pathology

Definition

Breast cancer = malignant tumor arising from breast epithelium
Most commonly ductal or lobular origin
Most common cancer in women worldwide
Major cause of cancer-related death in women
Rare in men, but male breast cancer exists and is usually treated with the same oncologic principles

Risk Factors / Etiology

Age: risk increases with aging
Female sex
Family history of breast/ovarian cancer
Genetic mutations:

BRCA1, BRCA2
PALB2, TP53, PTEN, CHEK2 in selected families

Hormonal/reproductive factors:

Early menarche
Late menopause
Nulliparity or late first pregnancy
Hormone replacement therapy

Previous chest radiation exposure
Previous breast cancer or high-risk breast lesion
Dense breast tissue
Lifestyle/metabolic factors: obesity after menopause, alcohol, smoking, physical inactivity

Pathological Classification

Invasive / infiltrating breast cancer

Invasive ductal carcinoma / invasive carcinoma NST → about 70-80%
Invasive lobular carcinoma → about 10-15%
Special types: tubular, mucinous, medullary-like, papillary, metaplastic
Inflammatory breast cancer = aggressive clinical form with dermal lymphatic invasion

In situ lesions

DCIS = ductal carcinoma in situ: malignant ductal cells without basement membrane invasion
LCIS / lobular neoplasia = risk marker and non-obligate precursor, often incidental

Paget disease of nipple

Malignant glandular cells in epidermis of nipple/areola
Usually associated with underlying DCIS or invasive cancer

Molecular / Biomarker Classification

Subtype	Typical markers	Treatment relevance
HR-positive / HER2-negative	ER and/or PR positive, HER2 negative	Endocrine therapy central; chemo according to risk/genomic tests
HER2-positive	HER2 overexpression/amplification	Anti-HER2 therapy + chemotherapy
Triple-negative	ER negative, PR negative, HER2 negative	Chemotherapy central; immunotherapy/targeted therapy in selected settings

Spread

Lymphatic spread:

Axillary lymph nodes most common
Internal mammary nodes
Supraclavicular/infraclavicular nodes

Hematogenous metastases:

Bone
Liver
Lung/pleura
Brain

II. Diagnostics and Staging

Triple Assessment / Triple Diagnosis

Clinical assessment
Imaging
Tissue diagnosis

All suspicious breast lesions need concordance between clinical, imaging and pathology findings
Discordant results → repeat biopsy or surgical diagnostic excision

Clinical Assessment

History:

Duration and growth of lump
Pain or cyclicity
Nipple discharge: bloody/unilateral/spontaneous is suspicious
Nipple retraction or eczema-like change
Skin dimpling, redness, edema
Family history, previous breast disease, hormone exposure

Inspection:

Asymmetry
Skin changes, scars, visible mass
Nipple inversion/retraction
Peau d'orange, erythema, ulceration

Palpation:

Begin with normal/asymptomatic breast
Assess lump: site, size, shape, consistency, tenderness, mobility, fixation
Upper outer quadrant is common because glandular tissue is abundant
Palpate axillary, supraclavicular and infraclavicular nodes

Clinical Features

Often asymptomatic and detected on screening mammography
Painless breast lump
Nipple retraction
Bloody or serous nipple discharge
Skin dimpling, thickening or ulceration
Peau d'orange → lymphatic obstruction
Axillary lump → lymph node metastasis possible
Inflammatory breast cancer: diffuse erythema, edema, warmth, rapid onset; can mimic mastitis

Breast Imaging

Mammography

First-line screening test and key diagnostic test, especially age >40
Findings:

Mass lesion
Microcalcifications, especially DCIS
Architectural distortion
Asymmetry
Skin/nipple changes

Ultrasound

Useful in younger women and dense breasts
Differentiates cystic vs solid lesions
Evaluates axillary lymph nodes
Guides core biopsy

MRI

Not routine for every cancer
Useful for:

High-risk screening, e.g. BRCA carriers
Very dense breasts when extent unclear
Invasive lobular carcinoma extent assessment in selected patients
Multifocal/multicentric disease suspicion
Response assessment after neoadjuvant therapy
Implant evaluation
Occult primary with axillary metastasis

Biopsy and Pathology

Core needle biopsy = preferred diagnostic biopsy
Vacuum-assisted biopsy useful for microcalcifications/small mammographic lesions
FNAB is less used for primary diagnosis because it gives cytology only, not architecture/receptor profile
Pathology report must include:

Histological type
Grade
Invasion vs in situ disease
Lymphovascular invasion if in surgical specimen
Margins after surgery
ER, PR, HER2
Ki-67 proliferation index

Staging

TNM staging:

T = tumor size and local extension
N = regional lymph nodes
M = distant metastasis

Routine distant staging imaging is not needed for most asymptomatic early breast cancer
CT chest/abdomen, bone scan or PET-CT if:

Locally advanced disease
Clinically node-positive/high-risk disease
Symptoms or lab abnormalities suggesting metastasis
Before neoadjuvant systemic therapy in higher-stage disease

Genetic testing if young age, triple-negative cancer, strong family history, bilateral disease, male breast cancer or criteria suggesting hereditary syndrome

III. Treatment of Invasive Breast Cancer

General Principles

Treatment should be planned by multidisciplinary breast team
Decision depends on:

Tumor size/location and breast size
Multifocality/multicentricity
Nodal status
ER/PR/HER2/Ki-67 and grade
Age, menopausal status, comorbidities
Genetic risk and patient preference

Main modalities: surgery, radiotherapy, endocrine therapy, chemotherapy, targeted therapy, immunotherapy in selected cases

Surgical Treatment of Breast

Breast-Conserving Surgery (BCS)

Wide local excision / lumpectomy
Preferred for many early breast cancers if clear margins and acceptable cosmesis possible
Usually followed by whole-breast radiotherapy
Margin for invasive cancer: no tumor on ink
Oncoplastic techniques can allow wider excision with better cosmetic result

Mastectomy

Indications:

Large tumor relative to breast size
Multicentric disease
Persistent positive margins after attempts at BCS
Contraindication to radiotherapy
Patient preference
Risk-reducing surgery in selected genetic high-risk patients

Types:

Simple/total mastectomy → removal of breast tissue
Skin-sparing mastectomy → preserves skin envelope for reconstruction
Nipple-sparing mastectomy → selected patients, oncologically safe if nipple not involved
Modified radical mastectomy → mastectomy + axillary lymph node dissection

Immediate or delayed reconstruction should be discussed if mastectomy needed

Axillary Management

Sentinel lymph node biopsy (SLNB):

Standard for clinically node-negative invasive breast cancer
Maps first draining lymph node(s)
Lower lymphedema risk than axillary dissection

Axillary lymph node dissection (ALND):

Clinically node-positive disease not downstaged / heavy nodal burden
Selected patients with positive SLNB depending on surgery, radiation plan and nodal burden
Risks: lymphedema, shoulder stiffness, nerve injury

Modern axillary treatment is de-escalated when safe; not every positive sentinel node requires ALND

Radiotherapy

After BCS: usually whole-breast radiotherapy
Boost to tumor bed if high local recurrence risk
Partial breast irradiation possible in selected low-risk patients
After mastectomy if high-risk:

Large tumor
Positive margins
Multiple positive nodes, especially >=4
Chest wall/skin involvement

Regional nodal irradiation for selected node-positive/high-risk disease

Systemic Therapy by Biology

Hormone Receptor Positive Disease

Endocrine therapy reduces recurrence and mortality
Premenopausal:

Tamoxifen
Ovarian function suppression + tamoxifen or aromatase inhibitor for higher-risk patients

Postmenopausal:

Aromatase inhibitor: letrozole, anastrozole, exemestane
Tamoxifen if AI unsuitable

Genomic assays can help decide chemotherapy need in selected HR+/HER2-negative early cancers

HER2-Positive Disease

Anti-HER2 therapy improves prognosis
Trastuzumab is central
Pertuzumab added in selected higher-risk/neoadjuvant settings
Usually combined with chemotherapy
Monitor cardiac function because HER2 therapy can cause cardiotoxicity

Triple-Negative Breast Cancer (TNBC)

ER-negative, PR-negative, HER2-negative
Chemotherapy is main systemic treatment
Neoadjuvant chemotherapy often preferred for tumors >2 cm or node-positive disease
Immunotherapy can be used in selected high-risk early TNBC depending on protocol/availability
BRCA-associated disease may have platinum/PARP inhibitor relevance in selected settings

Neoadjuvant and Adjuvant Therapy

Neoadjuvant therapy = before surgery:

Shrinks large tumor to allow BCS
Treats clinically positive nodes and may downstage axilla
Preferred for many HER2-positive and triple-negative tumors >2 cm and/or node-positive
Response gives prognostic information; pathologic complete response is favorable

Adjuvant therapy = after surgery:

Reduces recurrence risk
Chosen by stage + biomarkers + patient factors
Includes endocrine therapy, chemotherapy, anti-HER2 therapy, radiotherapy and selected targeted agents

Metastatic Breast Cancer

Usually systemic/palliative treatment, not primarily surgical
Biopsy metastatic lesion if feasible to confirm diagnosis and reassess ER/PR/HER2
Local surgery/radiotherapy for palliation: bleeding, ulceration, pain, fracture risk, brain/spinal compression
Treatment depends on biology: endocrine/targeted, anti-HER2, chemotherapy, immunotherapy/targeted options

IV. DCIS, LCIS, Paget Disease and Follow-Up

Ductal Carcinoma In Situ (DCIS)

Malignant ductal epithelial cells without invasion through basement membrane
Non-invasive, but can progress to invasive cancer
Often detected by screening mammography as microcalcifications
May cause nipple discharge, rarely palpable mass

DCIS Classification

Comedo
Cribriform
Micropapillary
Papillary
Solid
Grade and necrosis are clinically important

DCIS Diagnosis

Mammography: clustered/linear/branching microcalcifications
US if mass or dense breast
MRI if extent uncertain or high-risk context
Core/vacuum-assisted biopsy confirms diagnosis
SLNB is not routine for pure DCIS after BCS
SLNB considered if mastectomy planned, large/high-grade DCIS or high suspicion of invasion

DCIS Treatment

Breast-conserving surgery + radiotherapy for most patients if clear margins possible
Preferred margin for DCIS treated with whole-breast RT: about >=2 mm
Mastectomy if extensive, multicentric, cannot obtain clear margins, or patient preference
Post-mastectomy RT usually not needed for pure DCIS with clear margins
Endocrine risk-reduction if ER-positive:

Tamoxifen, especially premenopausal
Aromatase inhibitor option in postmenopausal women

Lobular Carcinoma In Situ (LCIS) / Lobular Neoplasia

Derived from lobular epithelial cells without basement membrane invasion
Usually asymptomatic
No palpable mass, no nipple discharge usually
Often incidental on core biopsy
Mammography may be normal; no typical microcalcification pattern
IHC: E-cadherin negative/lost; DCIS is usually E-cadherin positive
Classical LCIS is mainly a marker of increased bilateral breast cancer risk, not an obligate cancer requiring mastectomy

LCIS Treatment

Classical LCIS:

Regular surveillance
Risk-reducing endocrine therapy: tamoxifen, raloxifene or aromatase inhibitor depending on menopausal status/risk
Risk-reducing mastectomy only for selected very high-risk patients

Pleomorphic/florid LCIS behaves more like DCIS → excision and MDT discussion

Paget Disease of the Breast

Rare breast cancer manifestation involving epidermis of nipple and areola
Associated with underlying DCIS or invasive carcinoma in most cases
Clinical features:

Eczema-like erythema/scaling/crusting of nipple
Itching/burning
Nipple retraction
Bloody or serous discharge
May have underlying palpable mass

Diagnosis:

Nipple/skin biopsy: large pale atypical Paget cells
Mammography + US
MRI if mammography/US negative but suspicion remains or extent unclear
Core biopsy of underlying lesion

Treatment:

BCS including nipple-areola complex + radiotherapy if localized and breast conservation feasible
Mastectomy if extensive/multicentric disease or unsuitable for BCS
SLNB if invasive cancer or mastectomy planned
Systemic therapy according to underlying tumor biology: endocrine, chemotherapy, anti-HER2 therapy

Follow-Up After Curative Treatment

Regular clinical follow-up for symptoms, recurrence, treatment toxicity and psychosocial issues
Annual mammography of remaining breast tissue
No routine CT/PET/tumor markers in asymptomatic early breast cancer follow-up
Manage endocrine therapy side effects, bone health and menopausal symptoms
Assess arm lymphedema and shoulder function after axillary treatment
Genetic counseling and family risk management when indicated

Exam focus: Diagnosis is triple assessment: clinical examination, imaging and core biopsy. Treatment is stage + biology based. Early invasive cancer often gets BCS + radiotherapy + SLNB, or mastectomy if breast conservation is unsuitable. ER-positive disease needs endocrine therapy, HER2-positive disease needs anti-HER2 therapy, and triple-negative disease is chemotherapy-sensitive with frequent neoadjuvant treatment.