Breast Cancer — Causes, Mammography, HER2, Chemotherapy & Survival Guide — Symptoms, Causes & Treatment | MyMedicPlus

Breast cancer is the most frequently diagnosed malignancy in women worldwide, with 2.3 million new cases and 685,000 deaths recorded in 2020 (WHO). It arises from malignant transformation of breast epithelial cells — most commonly originating in the terminal duct lobular unit. Invasive ductal carcinoma (IDC — no special type) accounts for 70–75% of cases; invasive lobular carcinoma (ILC) for 10–15%; and the remainder include medullary, mucinous, tubular, and metaplastic subtypes. Breast cancer is defined molecularly by receptor status — fundamental to treatment decisions: oestrogen receptor positive (ER+, 70–80%); progesterone receptor positive (PR+); human epidermal growth factor receptor 2 amplified (HER2+, 15–20%); and triple-negative breast cancer (TNBC — ER-, PR-, HER2-negative, 10–15%). The 5-year survival rate exceeds 90% for localised early-stage disease, falling to approximately 28–30% for metastatic (stage IV) disease — underscoring the critical importance of early detection through mammographic screening.

Breast cancer risk factors span reproductive, hormonal, lifestyle, and genetic domains. Genetic risk: BRCA1 (chromosome 17q21) mutation — 60–72% lifetime breast cancer risk; BRCA2 — 55–71% lifetime risk; TP53 (Li-Fraumeni syndrome), PTEN (Cowden syndrome), CDH1, PALB2, ATM, CHEK2 — intermediate penetrance genes. Overall, hereditary breast cancer accounts for approximately 10–15% of cases. Age: incidence rises steeply from age 40 and peaks at 50–70 years. Hormonal and reproductive factors: early menarche (under 12) and late menopause (over 55) — prolong oestrogen exposure; nulliparity (no pregnancies) and late first pregnancy (after 35); current use of combined hormone replacement therapy (HRT — 26% elevated risk per UK MWS; rapidly declines after stopping); combined oral contraceptive pill (small increase, returns to normal 10 years after stopping). Lifestyle: excess alcohol (relative risk 1.04 per 10 g alcohol/day — dose-dependent); obesity post-menopause (adipose tissue is the main source of oestrogen after menopause — BMI above 30 confers 30–60% increased risk); lack of physical activity; ionising radiation (chest irradiation — Hodgkin lymphoma treatment); dense breast tissue (mammographic density — 4–6-fold increased risk). Protective factors: breastfeeding (reduces risk by approximately 4.3% per 12 months of breastfeeding); multiparity; physical activity (30–50% risk reduction); maintaining healthy weight.

Symptomatic breast cancer presentations: painless breast lump (in 85% of cases — the most common presentation; a discrete, hard, irregular lump with ill-defined edges is more suspicious than a smooth, mobile lump); change in breast shape or size; skin dimpling, puckering, or tethering over a lump (caused by ligamentous involvement — Cooper's ligaments); nipple changes — new nipple inversion, nipple deviation, eczematous changes of the nipple or areola (Paget's disease of the nipple — associated with underlying ductal carcinoma in 95%); nipple discharge — especially unilateral, single-duct, bloodstained discharge; skin changes — peau d'orange (skin thickening resembling orange peel — caused by lymphoedema from dermal lymphatic invasion in inflammatory breast cancer — a rapidly progressive form); axillary lymphadenopathy (enlarged, hard lymph nodes in the armpit — may be the first presentation of breast cancer). Asymptomatic detection: increasingly breast cancers are detected on routine mammographic screening before causing symptoms — typically appearing as microcalcifications, a spiculate mass, or architectural distortion. Metastatic breast cancer symptoms: bone pain (most common site of metastasis — vertebrae, pelvis, ribs); breathlessness (pleural effusion, pulmonary metastases); neurological symptoms (brain metastases — headache, weakness, cognitive change); jaundice and right upper quadrant pain (liver metastases).

Triple assessment is the gold standard diagnostic approach — combining clinical examination, imaging, and pathological biopsy. Clinical examination: breast and axillary examination by a specialist; record size, shape, and mobility of any mass; assess lymph node involvement. Imaging: Mammography (2D or digital breast tomosynthesis — DBT): first-line imaging for women over 40; microcalcifications (clustered, linear, pleomorphic), spiculate or irregular masses, and architectural distortion are suspicious features. BI-RADS classification (0–6) standardises mammographic reporting. Ultrasound: essential for targeted assessment of palpable lumps in all ages; particularly important in women under 40 (denser breast tissue limits mammography); characterises masses (solid versus cystic; irregular versus smooth margins) and guides biopsy; assesses axillary nodes. MRI breast: highest sensitivity (95–99%) for breast cancer but lower specificity; indicated for BRCA carriers screening, lobular cancer (more multifocal), implant assessment, and staging high-risk lesions; not a first-line screening tool in the general population. Pathological biopsy: core needle biopsy (14–16G ultrasound-guided) — provides histological diagnosis; essential before treatment planning; samples must include: tumour type, grade (Bloom-Richardson grading 1–3); receptor status (ER, PR by immunohistochemistry — Allred score; HER2 by IHC and ISH/FISH); proliferation index (Ki-67); DCIS grade. Fine needle aspiration cytology (FNAC): less commonly used than core biopsy — gives cytological (not histological) diagnosis; useful for lymph node assessment. Staging: TNM classification (T — tumour size; N — regional node involvement; M — metastases); CT chest, abdomen, pelvis; bone scan or FDG-PET-CT for stage III–IV disease. Genetics: BRCA1/2 testing for patients under 40 at diagnosis, those with triple-negative breast cancer under 60, or family history meeting NICE criteria.

Treatment is guided by TNM stage, molecular subtype (ER/PR/HER2 status), Ki-67, age, menopausal status, BRCA status, and the patient's preferences — planned by a multidisciplinary team (MDT). Surgery: Wide local excision (WLE, lumpectomy) — removal of the tumour with a margin of healthy tissue + sentinel lymph node biopsy (SLNB); followed by radiotherapy to the conserved breast. Mastectomy — removal of all breast tissue; options include skin-sparing, nipple-sparing, or total; immediate or delayed breast reconstruction (implant, LD flap, DIEP flap). Axillary management: SLNB — uses radioactive tracer or blue dye to identify and remove the first draining ('sentinel') lymph node(s); if positive for macrometastasis, axillary lymph node clearance (ALND) or targeted axillary dissection performed. Radiotherapy: post-WLE whole-breast radiotherapy reduces local recurrence risk by two-thirds; post-mastectomy radiotherapy (PMRT) for high-risk features (4+ positive nodes, large tumour, close margins); regional nodal irradiation; hypofractionated schedules (40 Gy in 15 fractions over 3 weeks) are standard — equivalent to 50 Gy/25 fractions. Systemic therapy by subtype: ER+ (hormone receptor positive): adjuvant endocrine therapy — premenopausal women: tamoxifen 20 mg daily for 5–10 years (reduces recurrence by 40–50%; reduces mortality by 30%); postmenopausal women: aromatase inhibitor (letrozole 2.5 mg, anastrozole 1 mg, exemestane 25 mg daily) for 5–10 years (superior to tamoxifen in postmenopausal women). CDK4/6 inhibitors (ribociclib, palbociclib, abemaciclib) added to endocrine therapy in high-risk early breast cancer — abemaciclib reduces distant recurrence by 30% (monarchE trial). Neoadjuvant endocrine therapy (6 months) for postmenopausal ER+ to downstage large tumours enabling breast conservation. HER2+ breast cancer: trastuzumab (Herceptin) 18 cycles (monoclonal antibody targeting HER2) — reduces recurrence by 50% in HER2-amplified tumours; pertuzumab (dual HER2 blockade with trastuzumab — APHINITY trial); neratinib (extended adjuvant for high-risk HER2+); ado-trastuzumab emtansine (T-DM1 — antibody-drug conjugate — for residual disease after neoadjuvant therapy). TNBC (triple-negative): chemotherapy mainstay — anthracycline (doxorubicin, epirubicin) + taxane (paclitaxel, docetaxel) ± carboplatin; pembrolizumab (checkpoint inhibitor — PD-1 blockade) + chemotherapy for high-risk TNBC (KEYNOTE-522 — improved pCR and event-free survival); olaparib (PARP inhibitor) for BRCA-mutated HER2-negative early breast cancer (OlympiA trial — 42% relative reduction in recurrence). Neoadjuvant chemotherapy (NACT): increasingly used for TNBC, HER2+, or large ER+ tumours — allows assessment of treatment response and guides adjuvant therapy based on residual disease. Metastatic breast cancer: intent is disease control and quality of life, not cure. ER+ metastatic: CDK4/6 inhibitor + aromatase inhibitor (palbociclib/ribociclib + letrozole — first-line), or fulvestrant (oestrogen receptor degrader); elacestrant (selective ER degrader) for ESR1-mutated progression. HER2+ metastatic: trastuzumab + pertuzumab + taxane (first-line); T-DXd (trastuzumab deruxtecan) for subsequent lines — remarkable activity even in low-HER2 disease. TNBC metastatic: chemotherapy; sacituzumab govitecan (antibody-drug conjugate targeting TROP-2) for pretreated TNBC.

Local recurrence after breast-conserving surgery (ipsilateral breast tumour recurrence — approximately 5-10% at 10 years; managed by completion mastectomy; risk markedly reduced by adequate radiotherapy). Lymphoedema (chronic upper limb swelling from axillary lymph node dissection or radiotherapy — affects 15-20% post-ALND; requires lifelong compression garment therapy and physiotherapy). Metastatic spread to bone (most common distant site — pathological fractures, hypercalcaemia, spinal cord compression; bisphosphonate/denosumab for bone-targeted treatment), lung, liver, and brain (headache, seizures, focal neurology). Treatment toxicities: anthracycline-related cardiomyopathy (particularly with concurrent trastuzumab — echocardiographic monitoring required throughout); aromatase inhibitor arthralgia and bone density loss (bisphosphonate prophylaxis recommended); chemotherapy-induced peripheral neuropathy from taxanes; premature menopause from chemotherapy in premenopausal women (requires contraception counselling and HRT discussion). Psychosocial and body image complications: depression affecting 25-30% of breast cancer patients; altered body image and self-esteem following mastectomy; sexual dysfunction from oestrogen deprivation and treatment; post-traumatic stress.

Primary prevention: lifestyle modifications reduce modifiable risk — limit alcohol to below 14 units/week; maintain healthy body weight, particularly post-menopause (adiposity increases oestrogen levels); exercise 150 minutes per week (30–50% risk reduction); breastfeed where possible. Chemoprevention: women at high risk (5-year risk above 3% using Tyrer-Cuzick or Gail models, or BRCA carriers): tamoxifen 20 mg/day for 5 years (premenopausal — 38% risk reduction); raloxifene (postmenopausal); anastrozole or exemestane (postmenopausal — up to 53% risk reduction in IBIS-II trial). High-risk surgical prevention: BRCA1/2 carriers — risk-reducing salpingo-oophorectomy (RRSO) reduces breast cancer risk by approximately 50% in BRCA1 carriers; risk-reducing bilateral mastectomy reduces breast cancer risk by 90–95%. Screening (secondary prevention — early detection): UK: NHS Breast Screening Programme — 3-yearly mammography for women aged 50–71; US: varies by guideline — ACS recommends annual mammography from age 40–45; BRCA carriers and high-risk women: annual breast MRI + mammography from age 25–30. Monthly breast self-awareness (not rigid self-examination) — know your normal; report any new change promptly. Dense breast tissue: detected on mammography — significantly increases cancer risk and reduces mammography sensitivity; supplemental screening (ultrasound or MRI) may be recommended.

See your GP within 2 weeks (urgent referral) for: a new discrete breast lump; unexplained change in breast size or shape; skin dimpling, puckering, or redness of the breast; nipple inversion that is new; bloodstained or clear nipple discharge from a single duct; or hard, fixed axillary lymphadenopathy. Do not wait to see if a breast lump resolves over one or two menstrual cycles — all new breast lumps in women over 30, and any suspicious features in younger women, should be assessed promptly. In the UK, the 2-week wait (2WW) pathway ensures referral to a breast clinic within 14 days for suspected cancer. Seek emergency assessment for: rapidly progressive, painful, red, hot, swollen breast that does not improve with antibiotics in a week (may be inflammatory breast cancer, not just mastitis); neurological symptoms (headache, new weakness, visual changes) in a patient with known breast cancer (brain metastases); new-onset severe back or bone pain in a patient with breast cancer history (bone metastases, spinal cord compression).