GYN and GU cancers Flashcards
how would you describe GYN cancers?
cancers that affect tissue and organ of the female reproductive system
what do we know about ovarian, peritoneal, and fallopian tube cancers?
they all arise from the same set of cells
what are the risk factors associated with ovarian cancer? median age of dx?
age, early menarche (<12y), late menopause (>52y), HRT or fertility drugs, first pregnancy >30y, obesity
63y median age at dx
greater than 70% of people with ovarian cancer have:
stage III/IV disease
what genes are commonly associated with ovca?
BRCA1/2, STK11, RAD51D, MLH1, MSH2, EPCAM, BRIP1, RAD51C (also MSH6, PMS2, TP53)
what is the BRCA1/2 mutation prevalence in ashkenzai jewish ind with epithelial ovca vs. non-jewish ind
40% AJ vs. 10% non-AJ
what other gyn cancers are associated with mutations in BRCA1/2?
fallopian tube, primary preitoneal
what is the cumulative risk (up to 20y) for peritoneal cancer following oopherectomy?
3.9-4.3%
how do we screen for ovarian cancer? limitations?
CA-125 (poor sensitivity in early stages), pelvic exam, transvaginal U/S (poor sensitivity in early stage, cannot reliably distinguish benign from malignant changes)
insufficient evidence for pop. screening, low prevalence of ovca in gen pop, not cost-effective, appropriate screening is undefined
what factors decrease risks for ovca?
multiparity, breast-feeding, OCP usage, oophorectomy, tubal ligation – any time you STOP shedding ovary/oocyte tissue)
what ways can we try to prevent ovca?
chemoprevention: OCP (esp. young women with increased risk), limit infertility drug use, limit HRT
surgical: oophorectomy, bilateral tubal ligation (72% risk reduction when used with OCP)
what are the benefits and risks with prophylactic oophorectomy?
benefits: 80-96% risk reduction in high-risk women) -> **residual risk for peritoneal cancers & decreases brca risk in premenopausal women
risks: loss of endogenous estrogen (impact heart, bones, sexual function), the effect of HRT options, emotional risks
what is the risk of occult invasive cancer after preventative surgery?
3.4%
when should we consider RRSO with various mutations? what if they decline?
BRCA1 -> 35-40y
BRCA2 -> 40-45 (depends on FHx)
if decline: TVUS and CA-125 @ 30-35y but not considered sensitive or specific enough to recommend
what are the mean age of onset for ovca with BRCA1/2?
1: 48y (28-78y)
2: 50.6 (29-74y)
what recommendation can we make for ovca risk reduction in Lynch syndrome?
TAHBSO (remove uterus, ovaries, fallopian tubes, and cervix)
Changes in which genes should lead you to consider/recommend RRSO?
BRCA1/2, Lynch genes, BRIP1, RAD51C, RAD51D
what are the tiers of somatic variants?
I-IV I: STRONG clinical evidence II: potential clinical evidence III: VUS IV: benign or likely benign
How do PARP inhibitors impact cancer cells?
lead to an increase in dsDNA breaks by influencing the failure of ssDNA repair, arrest replication fork -> dsDNA breaks
when are PARP inhibitors available?
BRCA1/2 and PALB2 variants (inherited and somatic) for metastatic brca and ovca
when can we can pts access immunotherapy? benefits?
indicated for Lynch syndrome and MSI-high tumors
first drug not limited to tumor location but rather indication of MMRD
what are some of the risk factors for uterine and endometrial cancers?
obesity, age, class/race/FHx, irregular menstrual periods, early menarche or late menopause, low or nulliparity, infertility, diabetes, hypertension, estrogen replacement therapy and/or tamoxifen, hereditary predisposition
what are some symptoms of uterine and endometrial cancers? how does it’s progression/dx compare to ovca?
unusual vaginal spotting, bleeding, discharge, pain in the pelvic region, presence of a lump
typically earlier onset which leads to a better prognosis
what are the various types of hysterectomy?
partial: only uterus
total: uterus and cervix
radical: uterus, cervix, vagina, ovaries, fallopian tubes
how can we treat uterine and endometrial cancer?
radiation, chemo, hormonal therapy
what’s the prognosis of endo/uterine cancers?
majority is stage 1 or 2. makes treatment easier
% of various cancers that are hereditary?
9% uterine 12-14% brce 14% prostate 10% crc 24% ovca
what parts of the body are GU cancers impacting? ex?
affect part of the body that play a role in reproduction and getting rid of waste products in the form of urine or both
ex: prostate, renal, renal pelvis and ureter, blader, testicular, penile, Wilms tumor
what is the most cancer dx in men in the US?
prostate cancer (1:5 lifetime probablity)
what is different about prostate cancer in African American men compared to others?
higher incidence and higher mortality rate
what are some of the possible side effects of treatment for prostate cancer?
impotence and incontinence
what risk factors are associated with prostate cancer?
FHx - brother or father with prostate cancer more than doubles a man’s risk of developing prostate cancer/risk is higher for men with multiple affected relatives esp if they were young at the time of dx
diet: high red meat or high-fat dairy products and low in fruits and vegetables may raise risk
how can we screen for prostate cancer?
PSA w/ or w/o digital exam
tests cannot predict likelihood cancer will grow and spread if found
when should we consider testing someone for germline mutations for prostate cancer?
metastatic prostate cancer
higher grade prostate cancer (Gleason>7) AND close blood blood relative with any:
- Brca <50y
- ovac @ any age
- pancreatic cancer @ any age
- 2 or more brca, panc, or higher grade prostate cancer at any age
what is the germline mutation prevalence in individuals with prostate cancer?
1:10 (11.8% of men with met prostate cancer)
what are the most common types of renal cancers?
clear cell (60-75%)
papillary (5-15%)
chromophobic (5-10%)
collecting duct (<1%)
what are the risk factors associated with renal cell carcinoma?
hereditary: FHx, age (dx <46y vs. 64y in gen pop), sex (male preponderance)
general: obesity, cigarette smoking, alcohol, physical exercise (reduced), high blood pressure
how is Birt-Hoge-Dube dx? type of lesions? who often detects it?
10 lesions (at least on biopsy proven folliculoma)
folliculomas, trichodiscomas, acrochordons (skin tags)
often picked up by dermatology
what features do pts with BHD often have? gene?
oral mucose polyps and lipomas
multiple renal carcinomas (chromophobe and oncocytic - also clea cell and papillary in 9 and 2%)
pulmonary cysts
spontaneous pneumothorax
FLCN (17p11.2)
What is HLRCC? characteristics?
hereditary leiomyomatosis renal cell cancer
cutaneous leiomyomata, renal cancer, uterine fibroids (early-onset and multiple), leiomyosarcomas reported, can affect childbearing, papillary renal cel carcinoma
what is the major criteria for HLRCC? definitive dx?
multiple cutaneous leiomyomatas with at least on biopsy proven
positive germline FH mutation
what is HPRCC? characteristics?
hereditary papillary renal cell carcinoma
papillary renal cancer (10-15% of renal cancers), multifocal and bilateral, hereditary cases often overexpression of MET gene due to dups or activating mutations of MET
when does tuberous sclerosis present? what % are sporadic?
can show up in childhood and often picked up due to renal findings
60-70%
what are the major features of TSC? how many are needed for clinical dx?
facial angiofibromas or forehead plaques
notraumatic ungual or periungual fibroma
shagreen patch (35%)
multiple retinal nodular hamartomas, calcified subependymal nodule, subependymal giant cell astrocytoma, cardiac rhabdomyoma (single or multiple), Lymphangiomyomatosis and/or renal angiomyolipoma, cortical tubers
what is the most common symptom of TSC?
seizures (60-70%)
what are the urological implications of Lynch syndrome?
adrenocortical carcinoma, urothlial carcinoma, testicular cancer, upper tract urothelial carcinoma, prostate adenocarcinoma
what is the penetrance of VHL?
80-97%
what are the different types of VHL?
Type 1, 2, 2A, 2B, 2C
what features may direct us to VHL?
RCC <50y
HB of retina or CNS
adrenal PCC or extra-adrenal paraganglioma
+
mutliple kidney or panc cysts, endolymphatic sac tumors, papillary cystadenomas of the epididymis or broad ligament, neuroendocrine tumors of the panc
how likely are you to find a PV in a person that meets clincial criteria for VHL? what % de novo? break down of pathogenic variants?
roughly 100%
20% de novo
70% point, 30% complete or partial deletion
