Breast Cancer

A set of 35 vocabulary-style flashcards covering the pathology, risk factors, screening, molecular subgroups, and treatment modalities for breast cancer based on the lecture notes.

Invasive ductal carcinoma (IDC)

The most common type of invasive breast cancer, accounting for about $70\text{--}80\%$ of cases, which spreads through the ducts to other parts of the breast.

3 pathology types

• Invasive ductal carcinoma (IDC)

• Invasive lobular carcinoma (ILC)

• Ductal and lobular carcinoma in situ (DCIS/LCIS)

Invasive lobular carcinoma (ILC)

A type of invasive breast cancer that spreads through the lobules to other parts of the breast and accounts for approximately $10\%$ of cases.

DCIS and LCIS

Non-invasive forms of breast cancer, officially Ductal and lobular carcinoma in situ, which are limited to the ducts or lobules and have not spread to surrounding tissue.

Masterectomy is crative in >95% of patients

Developed countries incidence

Breast cancer rates that are around $3\text{--}5\times$ higher than in developing countries, with the UK having approximately $94/100\text{k}$ cases compared to India's $26.6/100\text{k}$.

NHS screening interval

The frequency and age range for invitations to mammograms, occurring every $3$ years from age $50$ up to $71$.

Symptoms

• New lump or thickening in breast or underarm should be evaluated

• Swollen lymph glands in the armpit can rearely indicate breast cancer (often related to infections)

• changes in breast appearance (size, shape, feel)

• nipple discharge - fluid leaking from non-pregnant or breastfeeding woman

• nipple changes - any changes in position or appearance should be noted

Risk factors

• Age: women over 50

• Family history

• lifestyle (alcohol, diet, physical activity)

• environmental (radiation and chemical exposure)

Role of hormones

• Imbalances: imbalances such as menopause and infertility can increase risk

• menstrual cycle: women who start menstruating early or have late menopause onset, or have never given birth can increase factor

• use of HRT after menopause can increase risk

• oral contraceptives can increase risk

male breast cancer

• ~1% of all breast cancers

• presents later due to low symptom awareness

• risk factors:

  • age

  • klinefelter syndrome

  • testicular disorders

  • obesity

  • family history &. BRCA2 mutations

  • radiation

• most are ER-positive ductal carcinomas

• treated similarly to post-menopausal female breast cancer

Sporadic breast cancer

most common form of BC, arises by chance without family history and wiwthout BRCA1/2 mutation

• hormone exposure is major risk factor

• hormone exposure exposure increases the number of target cells by stimulating breast growth

• by driving proliferation, hormones also place cells at risk for DNA mutations

• metabolites of oestrogen can also directly cause mutations or generate DNA-damaging free radicals

Familial breast cancer

• about 5-10% of breast cancers are hereditatry due to mutations

• BRCA1&2 responsible for 80-90% of these,also rasing risk for ovarian, prostate and pancreatic cancers

• BRCA1&2 mutations are present in ~1 in 400 of general population

BC screening

NHS invites mammograms overy 3 years from age 50-71, over 71 may self refer

Screening results

Either mammography (M) or ultrasound (U).

M1/U1 - normal breast tissue

M2/U2 - benign (not cancer)

M3/U3 - abnormal or uncertain but prob benign

M4/U4 - suspicious and possibly cancer

M5/U5 - cancer

Aspiration Cytology (FNA)

A diagnostic method using a needle to sample cells from a suspicious area, such as enlarged lymph nodes, which is less invasive than surgical or core biopsies. Aided by imaging. C1 - C5

Needle core biopsy

The diagnostic gold standard for most suspicious breast lesions, enabling full histological assessment, tumor grading, and biomarker status.

• Low complciaction risk

• Higher diagnostic sensitivity than FNA

Surgical biopsy (lumectomy)

• Removal of a larger sample of breast tissue through surgery

• General anesthesia used to minimize discomfort

• Increased accuracy of diagnosis

• Invasive procedure

• Potential for discomfort, pain, and scarring

• Need for recovery time and follow-up care

Molecular subgroups

Most breast malignancies are adenocarcinomas (>95%). 3 major bologic subgroups with different responses and outcomes

• Hormone Receptor Pos/ HER2-neg (luminal) - ~70% cases

  • Luminal A

  • Luminal B

• HER2 enriched - ~15% cases

• Basal like/ triple neg breast cancer (TNBC) - ~ 10-15% cases

Luminal A

A hormone receptor-positive molecular subgroup characterized by slow growth, strong positive hormone status, and a better prognosis, representing $50\text{--}60\%$ of luminal cases. Less agressive

Luminal B

A hormone receptor-positive subgroup (~$10\%$ of luminal cases) that has a faster growth rate and more aggressive behavior compared to Luminal A. poorer prognosis, lower expression of hormone receptors

Biomarkers and targeted therapies

• ER/ PR positive → CDK4/6 inhibitors

• HER2 over expression → IHC 2+ (confirm with FISH)

• Ki-67 proliferation index → measures % of cycling tumor cells

• PD-L1 expression (TNBC) → identifies candidated for immunotherapy

Nottingham Histologic Score

A grading system used for breast cancer that evaluates tubule formation, nuclear pleomorphism, and mitotic count.

• Prognostic factors include tumor stage (TNM score) and the underlying biology

• the five stages 0 - IV are highly correlated with survival

OSNA

One Step Nucleic Acid Amplification; a molecular detection method used intra-operatively to analyze entire lymph nodes for metastases.

• Detects cytokeratin 19 (CK19) mRNA exression, an epithelial cell marker not normally present in lymph node tissue

• high sensitivity

Cytokeratin 19 (CK19)

An epithelial cell marker mRNA analyzed by OSNA, which is normally absent in lymph node tissue and indicates the presence of metastatic cells.

ctDNA (Liquid biopsy)

The analysis of circulating tumour DNA from a blood sample used for non-invasive genetic profiling and early prediction of relapse.

• can monitor treatment response and emerging resistance mutations

• emerging clinical tool- promising but not yet routine

Treatment of localised breast cancer (stage I, II, operable stage III)

• Surgery

• Radiotherapy

• Adjuvant chemotherapy - consider if high grade, HER2-pos or large tumor

• HER2- targeted therapy: trastuzumab (Herceptin), given with/ after chemotherapy for ~1 year

• Endocrine therapy (ER/PR) - tamoxifen or aromatase inhibitors, started after chemotherapy

• Neoadjuvant chemotherapy - for large or advanced tumors to downstage before surgery

PD-L1 expression

A biomarker used in Triple-Negative Breast Cancer to identify patients who candidates for immunotherapy such as Pembrolizumab.

Ki-67 proliferation index

A measurement of the percentage of cycling tumour cells within a sample used to determine the rate of tumor proliferation.

Stage IV (Metastatic) Survival

A stage of invasive carcinoma with distant metastasis present, yielding a $10$-year survival rate of $5\text{--}2500$.

HER2 confirmatory testing (IHC 2+)

A diagnostic protocol where cases with an IHC score of $2+$ must be further confirmed using FISH (fluorescence in situ hybridization) for gene amplification.

ER positive genomic pathways

Characterized by alterations such as $1\text{q}$ gain, $16\text{q}$ loss, and mutations in the PIK3CA gene.

treatment of inoperable/ metastatic cancer

• First-line endocrine therapy - for luminal A disease without major organ compromise

• Fisrst line chemotherapy - anthracycline based regimens for luminal B when liver/ling is present

• HER2-targeted therapy - trastuzumab, usually combines with chemotherapy

• Surgery (palliative) - for complications such as ulcerating breast masses, spinal cors compression or lung metastases

• radiotherapy (palliative) - effective for bone pain, primary tumor symptoms or brian metastases

• Bone-modifying agents: bisphosphonates

Overall goal: systemic disease control, prolong survival and optimise QoL rather than cure

AI-assisted mammography

A decision-support tool that highlights subtle abnormalities like microcalcifications and small masses to improve cancer detection and screening efficiency.

• AI tools help with automated mitotc counting, tumor grading and subtype prediction

• decision support tool only, augments but does not replace clinician judgement

Secondary high-risk genes

Mutations in genes such as CHEK2, TP53, PTEN, and LKB1/STK11 that account for less than $10\%$ of hereditary breast cancers.

summary