Ovarian/Endometrial Cancer (Dr. Remmenga) Cases: 1.

Ovarian Cancer - "silent killer" because no symptom complex to make you think of ovarian ca Pt who is 55 yo female (Avg age of ovarian ca) presents with lots of gas, flatulence, weight gain, loss of appetite, and not feeling well. - This could be IBS, but could be ovarian cancer! Ask her FMHx (history of breast or ovarian ca because assoc with BRCA1/2 mutation) note 5-10% have BRCA1/2 mutation, ask about adenocarcinoma (b/c have risk of development of other cancers) - Lifetime risk is 1/70, but risk of death is 1% from ovarian ca (1 per 100) - If one relative with ovarian ca --> 1/20 risk - If two relatives with ovarian ca --> 1/7 risk - If BRCA mutation --> 1/2 risk (due to variable penetrance) About 10% of ovarian tumors are mets (Krukenberg tumor - classically from the stomach - has signet ring shape) Ask about SH - Pregnancy assoc with ovarian ca --> if nulliparous (from theory of incessant ovulation); can do OCPs as preventive strategies (use for 5 years age 60% reduction in risk of ovarian cancer) Ask about symptoms: - Classic presentation is "I feel bloated and my clothes are getting tighter" - Ask about diet - they have early satiety " eat four to five bites and suddenly feel full" On PE look for: - Fixed pelvic mass via bimanual examination - more likely malignant if hard mass - Must r/o endometriosis (irregular mass) - Do U/S: look for cystic vs solid vs complex mass; size >6-8cm is malignant; bilateral involvement is more likely malignant; see lots of ascites = malignant - Other things on imaging that can help: omental cake (tumor goes into momentum) 3 types of ovarian cancer Epithelial ovarian cancer - mostly what we talk about Stromal tumors Sex-cord/Germ cell tumors Ovarian ca cause of death: bowel obstruction and starvation (because ovarian tumors commonly seed the peritoneum and acts like superglue and makes everything stick together leading to obstruction). Testing:

Besides CT, U/S - Look for CA125 (glycoprotei tumor marker assoc with inflam, not for screening because it can be high with PID, endometriosis, pregnancy, other cancers like breast and pancreatic) - 80% of non-mucinous ovarian cancers make CA125 - NO correlation with staging of tumor - Other screening tests: not really any that fit criteria (high sense, low cost, reproducible, have available treatment options) - therefore based on symptoms, FMHx, and PE Take pt to OR because we think she has ovarian ca - Do open-laparotomy and do a debunking procedure (reduce the tumor volume to nodules <1cm in size or if possible microscopic dz) - reason to do this is because chemo can work better with smaller tumor size and this has a better prognosis - take out colon, small bowel, lymph node, etc resection to make sure we take care of the disease, but also try to preserve GI tract as much as possible. Can prevent colostomy with EEA. If pt has carcinomatosis everywhere when you open them up what do you do? close them up. After surgery what do you do? Do chemotherapy (std of care is platinum based regimen with taxmen - ex: paclitaxel with carboplatin) --> 80% respond to this regimen Give 6-8 cycles of chemotherapy. 20% that don't respond have poor prognosis because if they don't respond to chemo, they then won't respond to anything. If CA125 goes down to <10 then it's a good prognostic factor. What other things to do with f/u (See them frequently in first two years post because 75% of cancers recur within 2 years): - check CA125 if it was elevated to begin with - Do physical exam and talk to pt about their symptoms (they can have same symptoms as before) - Do selective imaging based upon findings (if they have symptoms) - don't do routine imaging because radiation exposure and cost If CA125 increased in our patient with sx and mass, what do you do? - <6 mo poor prognosis - 6 to 12 mo : intermediate prognosis - >12 mo: better prognosis and likely to respond better to chemo to improve quality of life Can do intraperitoneal chemotherapy. Data showed that intraperitoneal therapy have

higher toxicity, but it showed a 16 month difference (benefit) compared to traditional chemo regimen. Newer chemo therapies: - looking at targeted therapy for specific processes involved in the disease eg bevucizimab aka AVASTIN (developed for colon cancer) -- it's anti-VEGF - had additional 4 month progression-free survival (but it's VERY expensive), and likely that it's NOT going to affect overall survival. 23000 new case, but 16000 die. Ovarian ca are stage 3 or 4 at time of dx. ENDOMETRIAL CANCER MC cancer of female organs in US (more new endometrial cancer) Type 1: estrogen excess (85% of endometrial cancers in US) Type 2: Seen in older women, thinner women, genetic predisposition, clear cell/MMT/serous - all have poor prognosis, not estrogen responsive Type 1: MCC is estrogen excess for Type 1 (obesity, iatrogenic - giving estrogen without progesterone). Lifetime risk in US of developing endometrial cancer: 1/40 (2.5%) If women 50lbs over ideal weight: 10x increased irsk Early 50s, obese, white/western european, non-smoker (weak benefit of smoke), nulliparous, may have PCO Risk factors: HONDA HTN Obesity Nulliparity Obesity Diabetes Age (increased) Screening for endometrial cancer: the patient says they have abnormal bleeding -->They need biopsy Can also do U/S. Don't need to do biopsy if streak is <4mm, but could still have Type 2. therefore if continued bleeding do sample. H-scope is more expensive so don't do. Endometrial biopsy shows tumor, grade 1 adenocarcinoma. - How to evaluate them? Do lab tests to see if metastatic - Do CXR (b/c common to have mets to lungs!)

- Take to OR --> take hysterectomy, oophorectomy and lymph nodes from iliac, vena cave and aorta. And surgical stage the patient. Pt may need any, all, or none of the additional treatment based on factors: - Chemo - Radiation - HRT - Observation Factors that impact treatment options include: histopathology (MMT, clear cell, serous), high stage (lymph node mets), grading (Grade 1 is innocuous, grade 3 tend to be highly aggressive) If out pt completes radiation therapy, then do surveillance (q3 months for 2 year because 75% of recurrences occur in 2 years, then every 6 months for 3 years, then just once a year after). After 5 years, only 1.5% risk of recurrence. Better outcomes compared to ovarian tumors. SARCOMAs: 2% of uterine cancers. Really bad tumor. Boards Pearl -- *Classic presentation: "rapidly enlarging uterine mass in postmenopausal woman" Tend to resistant to radiation and chemotherapy. So only hope is initial surgery.

Side note: E1 (Estrone): adipose tissue (peripheral conversion) E2 (Estradiol): ovaries E3 (Estratriol): placenta