Breast and Prostate Cancer

What signs and symptoms are clues for breast cancer

Firm, irregular fixed mass, pain less, skin dimpling, lymphadenopathy, spiculation, irregular shape, microcalcification

Why are mammograms and ultrasounds both used for breast cancer imaging

Mammogram is good for detecting mass, spiculation, microcalcification

Ultrasound good to diff cystic from solid mass, look at axillary lymph node

What is CT used for in cancer imaging

Used for N staging of cancer

Has poor characterization → Not used to screen

Why is CNB preferred to FNA in breast cancer

CNB gets both tissue and cells → Used for patho testing to look at architecture, invasion, histology etc

What is CA 15-3 and its use

Used to monitor breast cancer NOT for screening; false pos can be from benign liver and breast disease

BRCA1 function and relation to breast cancer

BRCA1 maintains genomic stability by repairing DNA strand break + cell cycle checkpoint → LoF means higher DNA breaks → NHEJ → Genomic instability

What is ER and PR

Estrogen and progesterone receptor → Indicates if tumor growth is hormone mediated

What is HER2

Receptor tyrosine kinase → Indicates tumor growth from overactivation of TK pathways (mTOR pathway)

What is Ki-67

Measure of active cell division → If >30% is high, 15-20% is low; Higher Ki has better response to chemo

ER driven proliferation in breast cancer

Estrogen bind to ER → Creates ERE → Transcription → Cancer cell growth

Why is tamoxifen used for breast cancer treatment in ER positive tumor

Tamoxifen is ER antagonist → Estrogen cannot bind = no tumor growth

Will cause menopause like symptoms in premenopausal woman

How do anthracyclines inhibit tumor growth

DNA intercalation, Topoisomerase II inhibition, ROS production

Action of taxanes on tumor growth

Bind to beta tubulin → Prevents tubulin disassembly in anaphase → Stuck in metaphase → apoptosis

Why is local and systemic therapy combined for breast cancer treatment

Local removes primary tumor and radiation of margin; systemic gets rid of possible micrometastasis that was missed in local therapy

Why is PSA used as a tumor marker

PSA high in CA prostate due to disrupted glandular architecture → it is prostate specific but not CA specific

Why is MRI used to evaluate prostate CA instead of ultrasound

MRI is good for soft tissue → Look at prostate anatomy, lesion, characteristic etc

What is the basis of positive bone scan in prostate CA Px

increased osteoblastic activity → CA prostate is closely related to bone metastasis

How is AR signaling changed in CA prostate

Normal: Testosterone → 5-DHT → AR binding → Conformational change → ARE in nuclei → Prostate growth and cell survival, diff etc

CA: Dysregulated signal → Change expression → Androgen synthesis is amplified → Increased cell survival and growth

Mechanism of TMPRSS2-ERG gene fusion and CA prostate

ERG is fused to TMPRSS2 → TMPRSS2 activated by androgen → ERG is now also androgen activated → abnormal cell transcription

How does loss of PTEN and activation of PI3K/AKT/mTOR pathway cause prostate cancer progression

PTEN convert PIP3 → PIP2 instead of AKT → Inhibit PI3K

PTEN loss = increased PIP3 → Increased AKT → mTOR increase → Protein synthesis

BRCA2 mutation and prostate cancer relation

BRCA2 help in DNA repair → Mutation = repair loss → Genomic instability → CA development

What is the action of GnRH antagonist and prostate cancer

GnRH cause LH release → LH stimulate Leydig → Testosterone production

GnRH antagonist → Block GnRhr → Low LH → Low testosterone → Low AR stimulation → Cancer growth slows

Action of abiraterone and enzalutamide

Abiraterone → Inhibit CYP17A1 → Lower androgen synthesis

Enzalutamide → Act on AR to stop signaling

Denosumab action

Inhibit RANKL → RANK activation decrease → Osteoclast activity decrease → Lower bone resorption

Opioid action in cancer pain relief

Lower cAMP and K channel opening → Hyperpolarization + Ca channel inhibition → Lower neurotransmitter release → Lower transmission of pain signal = lower pain