Hormone Replacement Therapy/Hormone Therapy
Hereditary Nonpolyposis Colorectal Cancer
Tamoxifen-Treated Women

Hormone Replacement Therapy/Hormone Therapy

There is no evidence to suggest that screening women prior to or during estrogen-progestin replacement therapy (HRT), also known as hormone therapy (HT), would decrease endometrial cancer mortality.[1,2] Women should have a prompt diagnostic work-up for abnormal bleeding. There is conflicting evidence regarding the endometrial thickness (ET) threshold that should be used for women taking HRT/HT. Most studies investigating ET thresholds for screening purposes have excluded women with a history of taking HRT/HT. A group of researchers studied 238 postmenopausal women on oral HRT/HT in an effort to characterize the endometrium of the HRT/HT user with transvaginal ultrasound (TVU). The mean ET was 5.4 mm (SD 2.9) for women using HRT (2 mm thicker in women using sequential HRT/HT than in women using continuous HRT/HT).[3] The study did not include a comparison group of non-HRT/HT using women, however, the ET measurements can be compared with other reports of ET in women who do not have a history of HRT use. For example, the mean ET for normal women who did not use HRT in another study was 6.2 mm (SD 4.2).[4] Some studies suggest that similar cutoff points can be used for ET thresholds regardless of HRT/HT use,[5] while others report increased endometrial thickening in women taking HRT/HT (without increased risk of endometrial cancer).[6]

The lifetime risk of endometrial cancer for women who meet the criteria for hereditary nonpolyposis colorectal cancer (HNPCC) or are at high risk for HNPCC is up to 60%. Unlike sporadic cases of endometrial cancer that tend to be diagnosed during the sixth and seventh decades of life, the mean age of endometrial cancer diagnosis in HNPCC is during the fifth decade, similar to colorectal cancer in frequency and age of onset.[7-10] Based on limited evidence, it appears that 5-year survival among HNPCC women diagnosed with endometrial cancer is similar to that of nonhereditary cases in the general population.[11] International guidelines suggest gynecologic surveillance including annual TVU with endometrial biopsy for women aged 25 to 35 years.[12,13] The most recent American Cancer Society Cancer Detection Guidelines (updated January 2005) recommend annual screening with endometrial biopsy beginning at age 35 years.[14]

Because the risk of endometrial cancer is increased in women who are treated with tamoxifen and even more increased in that subset of women who have a history of prior estrogen replacement therapy,[15] the question has been raised as to whether special surveillance is required.[16] Beyond a routine gynecologic examination eliciting any history of abnormal bleeding, it has been recommended that screening studies and procedures for detecting endometrial pathology in women taking tamoxifen should be left to the discretion of the individual gynecologist.[17] More importantly, any abnormal uterine bleeding should be completely evaluated.

Endometrial cancers that occur in this population are very similar to those cancers occurring in the general population, with respect to stage, grade, and histology.[18-20] Prognosis tends to be good and early detection does not appear to improve outcome.[21]

To date, there have been no published studies evaluating the effect of endometrial cancer-screening modalities on mortality among women taking tamoxifen for breast cancer treatment or prevention.

References

1. ACOG committee opinion. Routine cancer screening. Number 185, September 1997 (replaces no. 128, October 1993). Committee on Gynecologic Practice. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 59 (2): 157-61, 1997.  [PUBMED Abstract]
   
   
2. Korhonen MO, Symons JP, Hyde BM, et al.: Histologic classification and pathologic findings for endometrial biopsy specimens obtained from 2964 perimenopausal and postmenopausal women undergoing screening for continuous hormones as replacement therapy (CHART 2 Study). Am J Obstet Gynecol 176 (2): 377-80, 1997.  [PUBMED Abstract]
   
   
3. Van den Bosch T, Van Schoubroeck D, Ameye L, et al.: Ultrasound assessment of endometrial thickness and endometrial polyps in women on hormonal replacement therapy. Am J Obstet Gynecol 188 (5): 1249-53, 2003.  [PUBMED Abstract]
   
   
4. Bruchim I, Biron-Shental T, Altaras MM, et al.: Combination of endometrial thickness and time since menopause in predicting endometrial cancer in women with postmenopausal bleeding. J Clin Ultrasound 32 (5): 219-24, 2004.  [PUBMED Abstract]
   
   
5. Smith-Bindman R, Kerlikowske K, Feldstein VA, et al.: Endovaginal ultrasound to exclude endometrial cancer and other endometrial abnormalities. JAMA 280 (17): 1510-7, 1998.  [PUBMED Abstract]
   
   
6. Mossa B, Imperato F, Marziani R, et al.: Hormonal replacement therapy and evaluation of intrauterine pathology in postmenopausal women: a ten-year study. Eur J Gynaecol Oncol 24 (6): 507-12, 2003.  [PUBMED Abstract]
   
   
7. Watson P, Vasen HF, Mecklin JP, et al.: The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer. Am J Med 96 (6): 516-20, 1994.  [PUBMED Abstract]
   
   
8. Aarnio M, Sankila R, Pukkala E, et al.: Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81 (2): 214-8, 1999.  [PUBMED Abstract]
   
   
9. Vasen HF, Wijnen JT, Menko FH, et al.: Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 110 (4): 1020-7, 1996.  [PUBMED Abstract]
   
   
10. Dunlop MG, Farrington SM, Carothers AD, et al.: Cancer risk associated with germline DNA mismatch repair gene mutations. Hum Mol Genet 6 (1): 105-10, 1997.  [PUBMED Abstract]
    
    
11. Boks DE, Trujillo AP, Voogd AC, et al.: Survival analysis of endometrial carcinoma associated with hereditary nonpolyposis colorectal cancer. Int J Cancer 102 (2): 198-200, 2002.  [PUBMED Abstract]
    
    
12. Burke W, Petersen G, Lynch P, et al.: Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium. JAMA 277 (11): 915-9, 1997.  [PUBMED Abstract]
    
    
13. Vasen HF, Mecklin JP, Khan PM, et al.: The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 34 (5): 424-5, 1991.  [PUBMED Abstract]
    
    
14. Smith RA, Cokkinides V, Eyre HJ: American Cancer Society Guidelines for the Early Detection of Cancer, 2005. CA Cancer J Clin 55 (1): 31-44; quiz 55-6, 2005 Jan-Feb.  [PUBMED Abstract]
    
    
15. Barakat RR: Tamoxifen and endometrial neoplasia. Clin Obstet Gynecol 39 (3): 629-40, 1996.  [PUBMED Abstract]
    
    
16. Love CD, Muir BB, Scrimgeour JB, et al.: Investigation of endometrial abnormalities in asymptomatic women treated with tamoxifen and an evaluation of the role of endometrial screening. J Clin Oncol 17 (7): 2050-4, 1999.  [PUBMED Abstract]
    
    
17. ACOG committee opinion. Tamoxifen and endometrial cancer. Number 169, February 1996. Committee on Gynecologic Practice. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 53 (2): 197-9, 1996.  [PUBMED Abstract]
    
    
18. Fisher B, Costantino JP, Wickerham DL, et al.: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90 (18): 1371-88, 1998.  [PUBMED Abstract]
    
    
19. Barakat RR, Wong G, Curtin JP, et al.: Tamoxifen use in breast cancer patients who subsequently develop corpus cancer is not associated with a higher incidence of adverse histologic features. Gynecol Oncol 55 (2): 164-8, 1994.  [PUBMED Abstract]
    
    
20. Fornander T, Hellström AC, Moberger B: Descriptive clinicopathologic study of 17 patients with endometrial cancer during or after adjuvant tamoxifen in early breast cancer. J Natl Cancer Inst 85 (22): 1850-5, 1993.  [PUBMED Abstract]
    
    
21. Barakat RR, Gilewski TA, Almadrones L, et al.: Effect of adjuvant tamoxifen on the endometrium in women with breast cancer: a prospective study using office endometrial biopsy. J Clin Oncol 18 (20): 3459-63, 2000.  [PUBMED Abstract]
    
    

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