Mary Elina Ferris, MD, MSEd
Medical Director, Southern California
Associate Clinical Professor of Family Medicine
Clinical Associate Professor of Family Medicine

California Medical Review, Inc. (CMRI)
Loma Linda University School of Medicine
University of Southern California

Physiologic changes associated with aging have significant effects on drug activity in the elderly population. Case studies will be used to illustrate important principles of geriatric prescribing, as well as the factors that contribute to increase adverse drug reactions in the elderly. Experts have identified a number of potentially inappropriate drugs for use in the elderly, and these will be reviewed along with a discussion of possible alternatives. Finally, tips for effectively medicating the elderly will be presented.

Educational Objectives

• Review the Epidemiology of breast cancer, including high-risk groups
  
• Discuss the mammographic screening guidelines of the major professional groups
  
• Outline the possible uses for genetic screening of high-risk women

Case Examples (All females)

• 40 y.o. with 1.0 cm firm nodule in right breast no family history
• 70 y.o. with 3 cm fixed and irregular lump left breast for 2 years
• 35 y.o. with multiple cystic swellings in both breasts, family history of mother with breast cancer diagnosed at age 37
• 25 y.o. pregnant or lactating with new mass in one breast
• 18 y.o. with one marble-sized lump in breast

II. Incidence and Statistics

An estimated 2 million women will be diagnosed with breast or cervical cancer in the 1990s, and half a million will lose their lives. A disproportionate number of deaths will be among minorities and women of low income.

Breast cancer is the most common nondermatologic cancer among American women and is second only to lung cancer as a cause of cancer-related deaths in all ages. An estimated 180,200 new cases of breast cancer among women will be diagnosed in 1997, and 43,900 women will die from the disease.

For comparison, for cervical cancer the estimates are 14,500 new cases of invasive cervical cancer will be diagnosed in 1997, and 4,800 women will die from the disease.

• Breast CA is 32% of new cancer Dx
• Breast CA is #1 incidence for women but Lung CA #1 deaths
• Incidence increased 550% between 1950-1991
• Lifetime risk of Breast CA for US women:
  1991 -- 1 Out of 9 (110/100,000)
  1987 - 1 Out of 10
  1970 -- 1 out of 13
• Age-adjusted mortality relatively stable from 1930-present 22/100,009
• Early detection and aggressive treatment may "cure" 90% (Up to 80% of early cancers may have conservative Rx)
• 80-85% of new breast lumps are found in breast self-exams

II. Natural History of Breast Cancer

• Hormonally-induced malignancy, starts at puberty
  
• Normal ducts >> Intraductal Hyperplasia >> Atypia >>Invasion
  
• Risk stabilizes at Menopause if no Estrogen replacement

III. Screening

Breast cancer screening by mammography is the most effective method of detecting breast cancer in its earliest most treatable stage. Mammography detects cancer an average of 1.7 years before the woman can feel the lump herself and locates cancers too small to be felt during a breast examination.

Generally, survival has an inverse relationship with the stage of breast cancer at detection --- the more advanced the cancer stage, the lower the survival rate. When breast cancer is diagnosed at a local stage, the 5-year survival rate is 97%. When breast cancer is diagnosed at a distant stage (metastasized), the 5-year survival rate decreases to 20%.

a. Risk Factors

• Relative Risk and Age --- Specific Risk Interpretation
  
• Specific Risk Factors --- Myths and Realities
  Widely Accepted Risk Factors:
  Female gender
  Older age
  Residence in North America or Northern Europe
  a) Diet - YES?
  b) Postmenopausal Obesity - YES?
  c) Alcoholic Beverages - YES?
  d) Tobacco Use - MAYBE
  e) Reproductive History (Parity & Breastfeeding) - YES?
  f) Exercise - YES? (If early)
  g) Stress and Personality Type - NO
  h) High Socioeconomic Status - YES?
  i) Previous Ovarian or Endometrial Cancer - YES
  j) Environmental Microwave Exposures - NO
  k) Exogenous Hormones - YES? (Oral Contraceptives and Estrogen Replacement)
• Family History and Genetics
  a) First degree relative: 2-3 fold increased risk
  b) HIGHEST RISK: If woman < 50 y.o.,
  Relative with premenopausal diagnosis
• Previous Breast Pathology
  a) NO RISK:
  Fibrocystic changes
  b) PROVEN RISK:
  Atypical Intraductal & Intralobular Hyperplasia

b. Breast Self-Examination (BSE)

Although research fails to support the widespread usefulness of BSE promotion at the population level, many women continue to discover breast cancer through this technique and the American Cancer Society continues to support educating women in its use.

• BSE: The "new" approach (more positions, more thorough)
• Patient Education Techniques: "SHOW ME"
• Consider lubrication (e.g., liquid soap)
• PHYSICIAN DOCUMENTATION IF BSE NOT CONFIRMED:
  Pt complaint & dates, findings, follow-up
• GOAL: Find SUBTLE changes, < 1.5 cm critical size

c. Common Barriers to Screening

Fear: Women do not want to discover that they have cancer.

Cost: Many women cite cost as the reason they do not use early detection programs. Many are not aware of the availability of low-cost programs.

Transportation: Because many women lack transportation, the location of screening facilities is important.

Communication Barriers: Communication styles and methods are sometimes inappropriate to the needs of the women seeking services.

Lack of Physician Referral: Studies have shown that women are up to 12 times more likely to be screened if their physician recommends screening.

Lack of Child Care: Some women need assistance with arranging child care to be able to use screening.

IV. Summary of Screening Recommendations

a. Physical Breast Examination

(NOTE: 26% Sensitivity when performed by a clinician in Breast Cancer Detection Demonstration Project, JAMA 1987;257:2197-2203; Note 10% of breast cancers may be missed by mammography alone in this same project, CA 1982;32:194-225)

Women Under 40 Years of Age

• American Academy of Family Physicians -- Clinical breast examination should be performed every 1 to 3 years on women aged 30 to 39.

• American Cancer Society -- Women should have clinical breast examinations every 3 years from age 20 to 39 years.

• American College of Obstetricians and Gynecologists Women over age 18 years should have clinical breast examination during the periodic evaluation, yearly, or as appropriate.

• Canadian Task Force on the Periodic Health Examination and U.S. Preventive Services Task Force -- Physicians may elect to perform clinical breast examination on women under age 40 who are at high risk, especially those whose first-degree relatives have had breast cancer diagnosed before menopause.

• American Academy of Family Physicians, American Cancer Society, American College of Obstetricians and Gynecologists, and American College of Physicians -- Annual clinical breast examination should be performed on women 40 years of age and older.

• Canadian Task Force on the Periodic Health Examination and U.S. Preventive Services Task Force -- Clinical breast examination should be performed on women aged 50 and over every 1 to 2 years. Physicians may elect to perform clinical breast examination on women under age 50 who are at high risk, especially those whose first-degree relatives have had breast cancer diagnosed before menopause. These recommendations are under review.

b. Breast Self-Examination (BSE)

• American Academy of Family Physicians, American Cancer Society, and American College of Obstetricians and Gynecologists -- Recommend that clinicians encourage and teach women to examine their breasts every month. Clinicians may wish to instruct their female patients in breast self-examination.

• U.S. Preventive Services Task Force (USPSTF) -- No recommendation for or against inclusion of teaching BSE; data regarding effectiveness extremely limited, inferior accuracy and many false positives.

c. Mammography

• Mammography is the most effective means of early detection of breast cancer (Sensitivity 75-88%, Specificity 83-98.5%).

• There is controversy about whether it reduces mortality in women less than 50 years of age., namely that there is decreased sensitivity (10-15% lower for ages 40-49, and higher false positives 7-1O% for 4O-49 compared to 4.5-8%). There is also a lower yield for younger ages, with the number of diagnoses at first mammogram screening showing 3 breast cancers/l000 mammograms for ages 40-49 compared to 6/1000 for ages 5O-59. Yield for women aged 6O-69 is even better at 13/1000.

High Risk Women under age 50

• American Academy of Family Physicians, and American College of Obstetricians and Gynecologists -- Women with a family history of premenopausally diagnosed breast cancer in a first-degree relative should have mammography regularly beginning at 35 years of age.

• American College of Physicians -- Women 40 years of age and older who have a history of breast cancer or who are otherwise at increased risk should have annual mammography.

• Canadian Task Force op the Periodic Health Examination and U.S. Preventive Services Task Force -- Physicians may elect to recommend mammography starting at age 35 for women at high risk, especially those whose first-degree relatives have had breast cancer diagnosed before menopause.

• U.S. Preventive Services Task Force (USPSTF) -- No evidence specifically evaluating mammography in "high-risk" women in this age 40-49. Recommendation for screening should be made on other grounds: patient preference, high burden of suffering, and known higher incidence in the high-risk group.

Low Risk Women Age 40-49 years

• American Cancer Society, American College of Radiology, American Medical Association, and American College of Obstetricians and Gynecologists -- Should receive screening mammograms every 1 to 2 years.

• American Academy of Family Physicians -- Recommends counseling about potential risks and benefits of mammography (Policies dated 6/97).

• National Cancer Institute -- Revised previous opposition in 3/97 and now recommends screening mammograms every 1 to 2 years if women aged 40-49 are at average risk.

• U.S. Preventive Services Task Force (USPGTF) -- No recommendation regarding mammography age 40-49 due to conflicting evidence regarding clinical benefit; no evidence specifically evaluating mammography in "high-risk" women in this age group. Recommendation for screening should be made on other grounds: patient preference, high burden of suffering, and known higher incidence in the high-risk group.

All Women 50 Years of Age and Older

• American Cancer Society, American College of Radiology, American Medical Association, and American College of Obstetricians and Gynecologists -- Should receive screening mammograms every year.

• American Academy of Family Physicians -- Mammograms should be offered every 1-2 years for ages 50-69.

• National Cancer Institute -- Recommends a frequency of every 1 to 2 years. Over age 70 should be screened unless other health conditions would not warrant.

• American College of Physicians -- Recommends a frequency of every 2 years and STOPPING AT AGE 74.

• USPSTF and Canadian Task Force on the Periodic Health Examination -- Mammograms every 1 to 2 years for age 50-69 only. Limited and conflicting for use in ages 70-74, no evidence for use in age 75 and over. Suggests decisions about screening age 70 and over who have a reasonable life expectancy be based on other grounds such as high burden of suffering.

• American Geriatrics Society-- Recommends that women over 65 years of age receive mammograms at least every 2 or 3 years until age 85.

V. What's New in Breast Cancer Screening

a. Mammograms: Standardized Reporting System

• American College of Radiology: Breast Imaging and Reporting Data System (BI-RADS)
  
• Lesion Shape: Round, Oval, Lobular, Irregular
• Margins: Circumscribed, Microlobulated, Obscured, Indistinct or Spiculated
  
• Calcifications: Benign, Intermediate concern, High Probability of Malignancy
• Conclusions: Strict definitions of terms --Negative, Benign, Probably Benign, Suspicious, Highly Suggestive of Malignancy

b. Risk Factors: Ongoing Debates

Nulliparity, Abortions, Estrogen Therapy

c. Genetic Screening

• Estimates of Women with positive family history: 5-20%

• Known presence of highly prevalent breast cancer susceptibility gene

• Small subset of women with Inherited Mutations in genes BRCA1 and BRCA2 which confer 80% lifetime risk of breast cancer

• Not enough evidence yet to recommend widespread genetic screening

Clinical Outcomes Qf Case Examples (All Females)

1. 40 y.o. with 1.0 cm firm nodule in right breast, no family history
   BREAST CANCER

2. 70 y.c. with 3 cm fixed and irregular lump left breast for 2 years
   BREAST CANCER

3. 3 5 y.o. with. multiple cystic swellings in both breasts, family history
   BENIGN

4. 25 y.o. pregnant or lactating with new mass in one breast
   RULE OUT BREAST CANCER

5. 18 y.o. with one marble-sized lump in breast
   BENIGN

REFERENCES

1. Bland KI, Love N. Evaluation of Common Breast Masses. Postgrad Med 1992; 92(5): 95-112.

2. Donegan WL. Evaluation of a Palpable Breast Mass. N Engl J Med 1992; 327(13): 937-42.

3. Harris M et al. Breast Cancer (3-part Review Article). N Engl J M 1992; 327(5,6,7): 319-328, 390-398, 473-480.

4. Hoskins KF, Stopfer JE, et al. Assessment and Counseling for Women With a Family History of Breast Cancer. JAMA 1995; 273:577-585.

5. Kelly PT. Understanding Breast Cancer Risk. Philadelphia: Temple University Press, 1991. 157pp.

6. King, M-C Rowell S, Love SM. Inherited Breast and Ovarian Cancer. JAMA 1993; 269:1975-1980.

7. Mettlin C, Smart CR. Breast cancer detection guidelines for women aged 40 to 49 years: Rationale for the American Cancer Society reaffirmation of recommendations. CA Cancer J Clin 1994; 44(4): 248-255.

8. National Institutes of Health, National Cancer Institute. Screening Mammograms: Current Scientific Evaluation. NIH Publication No. 94-3835, 1994(July).

9. Philips RL, Garfinkel L, Kuzma JW, et al. Mortality Among Seventh-Day Adventists for Selected Cancer Sites. J Natl Cancer Inst 1980;65(5): 1097-1107.

10. Spicer DV, Pike CM. Breast cancer prevention through modulation of endogenous hormones. Breast Cancer Research and Treatment l993; 28(2):179-93.

11. U.S. Public Health Service. Clinician's Handbook of preventive Services. Washington, D.C.: Government Printing Office, 1994. 342pp.

12. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services, 2nd ed. Baltimore: Williams & Wilkins, 1996. 953pp.