OVARIAN NEOPLASMS

I. Benign

  1. Cystic
  1. Functional cysts
  2. Serous cystadenomas
  3. Mucinous cystadenomas
  4. Teratomas
  5. Endometrioma
  1. Solid
  1. Thecoluteal
  2. Fibroma
  3. Brenner tumor

II. Malignant

  1. 4% of cancers in women; 5% of cancer deaths in women
  2. Risk factors
  1. Family hx
  2. Low parity
  3. Infertility (possibly)
  4. Endometriosis (possibly)
  5. High fat diet
  6. Urban living
  7. Jewish ancestry
  8. Use of fertility drugs (e.g. clomiphene citrate or human menopausal gonadotropins)
    1. Some support for a connection in case-control studies, but
    2. A prospective study of 780 exposed women followed for avg. 18y found no evidence of an increased risk of ovarian Ca dx (Fertil. Steril. 71:853, 1999--JW)
    3. A meta-analysis of 8 case-control studies involving 5207 cases and 7705 controls, use of fertility drugs, after adjustment for fertility status, was not ass'd with risk for ovarian Ca (Am. J. Epidem. 155:217, 2002--JW)
    4. A retrospective cohort study of 12,193 women (mean age 30y) treated for infertility found no association between use of fertility drugs (either clomiphene or gonadotropins) (Obs. Gyn. 103:1194, 2004--abst)
  9. Use of Oral Contraceptives has been associated with reduced risk in case-control studies (e.g. Fertil. Steril. 82:186, 2004--JW)
  10. Using data from 375 general practices and over 1.1 million women, U.K. researchers derived and validated an algorithm for determining ovarian cancer risk in women 30-84yo with no known h/o ovarian Ca.  They identified independent predictors as including age, abdominal distention, family h/o ovarian Ca, abdominal pain, postmenopausal bleeding, loss of appetite, anemia, rectal bleeding, and weight loss.  The 10% of women with highest predicted risk accounted for 63% of all ovarian cancers diagnosed over the 2y surveillance period.  Area under ROC curve was 0.84. (BMJ 344:d8009, 2012-JW).
  1. Presenting symptoms--Unfortunately, these are highly non-specific
  1. Abdominal and/or pelvic pain and bloating
  2. Increased abdominal size
  3. Dyspepsia
  4. Urinary frequency and urgency
  5. Weight loss
  1. Tumor markers
    1. CA125 (about 80% sens/specific)
    2. Lysophosphatidic acid (LPA)--Click on link for details
  1. Epithelial adenocarcinomas
  1. Usually >40yo
  2. Most common is papillary serous cystadenocarcinoma
  1. Germ cell tumors
  1. Usually <40yo
  2. Mature vs. immature teratoma, mucinous cystadenocarcinoma
  3. 15% are bilateral
  4. Adjuvant chemo if advanced
  1. Sex cord/mesenchymal (often hormone-producing)--rare
  2. Metastatic to ovary--rare

III. Genetic markers for ovarian Ca risk

  1. BRCA1 and BRCA2-Click link for details
  2. Prophylactic oophorectomy associated with lower risk of ovarian Ca dx in two nonrandomized studies (NEJM 346:1609, 2002--JW; NEJM 346:1616, 2002--JW)

IV. Screening for ovarian Ca

  1. Serum CA125 levels (sensitivity  not very high; probably around 66%; also not very specific)
  2. Ultrasound
  3. CA125 + ultrasound
    1. 22,000 postmenopausal women > 45yo randomized to annual screening (serum CA125, u/s if elevated, and referral to Gyn if u/s abnormal) vs. usual care x 3y. Over 7y of f/u, median survival among those pts who developed ovarian Ca was sig. higher in the screened group (73mos vs. 42mos); however, the difference in mortality from ovarian Ca over the study period (0.8 vs. 1.6 per 1,000) did not reach statistical significance (Lancet 353:1207, 1999--JW)
    2. In a study in 78,216 women 55-74yo assigned to screening for ovarian Ca with (CA-125 Q1y x 6y + ovarian ultrasound Q1y x 4y) vs. no screening, over median 12.4y f/u, there was no sig. diff. in ovarian Ca-related mortality between the two groups ("Prostate, Lung, Colorectal and Ovarian ("PLCO") Cancer Screening Trial"; JAMA 305:2295, 2011-abst)
  1. Lysophosphatidic Acid
    1. May have better sensitivity for ovarian Ca than CA125 (ACS Meeting 5/99, cited in FP news 6/1/99)
    2. Elevated levels are highly sensitive though not perfectly specific for ovarian Ca (JAMA 280:719, 1998--JW)
  2. Leptin-prolactin-osteopontin-IGF2 levels
    1. In prospective validation trial in 106 healthy women and 100 women with ovarian Ca, a formula based on levels of these four serum proteins had sensitivity of 96% and specificity of 94% for ovarian Ca (Proc. Natl. Acad. Sci. USA 102:7677, 2005--JW)
  3. Proteomic biomarkers (patterns of protein expression)
    1. One such pattern, using five proteins (transthyretin, hemoglobin protein, apolipoprotein A-I, transferrin, and CA-125) was highly sensitive and specific in one small study (FP News 2006)