ACP: Breast Cancer Update

1
ACP Breast Cancer Update

• Elaine A. Muchmore, M.D.
• UC San Diego
• 10/20/07

2
Breast Cancer

• Breast cancer affects more than 150,000 women
  each year, with a lifetime incidence of greater
  than 10.
• Although there have been advances in genetic
  risks, these (BRCA1, BRCA2) mutations account for
  less than 5 of cases.
• Mortality has decreased, related to earlier stage
  at diagnosis, but is still 40,000/year in the
  U.S.

3
Discussion points today

• Screening strategies, and when to start
• Role of MRI in screening
• Role of aromatase inhibitors

4
Screening strategies when to start

• Multiple trials have demonstrated reduction in
  mortality by 30 in women ages 50-69 screened by
  mammography
• NIH consensus panel reviewed 8 trials that
  included women 40-49 no difference in mortality
  within 7 years of screening
• Trend toward decreased mortality if followed 10
  years (16-17) question whether benefit is from
  screening before or after age 50

5
What are the real issues?

• Breast cancer is the leading cause of death for
  women aged 40-49 in US
• A 40 yo has a 2 chance of DCIS or invasive
  breast cancer before age 50
• Mortality rate in black women is 50 higher in
  40-49 group than whites
• False negative mammograms in 40-49 group in 25,
  compared to 10 in 50-69 group
• False positive mammograms more common in 40-49
  group 30 of women will have abnormal mammogram
  between 40-50
• Subset analysis reveals that false negative and
  positive rates not significantly different in
  40-49 vs 50-59 groups.

6
Consensus panel recommendation

• Data currently available do not warrant a
  universal recommendation for all women in their
  forties.
• Sequelae
• Costs for screening have not been covered by HMOs
  and third-party payers
• Psychological burden (whether or not screening
  performed)
• Concern that black women may not be included and
  engaged in the controversies about medical care

7
Should you recommend screening for women at age
40?

• Yes for high risk, as defined by
• Positive test for BRCA 1/2 mutation in pt. OR 1st
  OR 2nd degree relative
• 2 cases in family of breast and/or ovarian cancer
• 20 likelihood of carrying mutation when tested
  by BRCAPRO
• Ashkenazi jewish descent with personal h/o breast
  cancer or 2 family members with same
• Yes for breasts difficult to examine (fibrocystic
  changes, dense)

8
Discussion points today

• Screening strategies, and when to start
• Role of MRI in screening
• Role of aromatase inhibitors

9
Breast cancer screening strategies

• Modality
• Exam (self or physician)
• Mammogram
• Ultrasound
• MRI

• Sensitivity
• Poor
• 38
• 25
• 85
• Exams all performed same time in pts with
  BRCA1/2 mutations (JAMA(2004) 2921317)

10
No free lunch costs of screening

• 236 high-risk women examined with exam, US,
  mammogram, MRI (JAMA 2921317, 2004). Strategy
  biopsy if 1 of 4 screening studies positive. Av
  age 47
• Results
• 22 breast cancers in 3 years
• 14 biopsies benign
• 2 cancers detected by mammogram alone, 2 by US
  alone, 9/12 not detected by exammammogram
  detected by MRI
• Conclusion all screening strategies required in
  high risk patients for maximum sensitivity

11
Costs of screening

• In another study of high-risk women (Radiology
  244381, 2007), 171 women screened with
  MRIUSmammogram. Av. Age45
• Results
• 60 positives
• 31 MRI only, yielding 4 CA
• 6 MRI, mammogram , yielding 1 CA
• 1 MRI, mammogram, US, yielding 1 CA
• Positives on MRIUS, only on US, mammogramUS
  yielded no cancers

12
MRI good and bad

• Good
• Definitely most sensitive screening modality
• Year 1 screens 85 sensitive for MRI, compared
  with 25 US, 38 mammogram
• (Specificity excellent with all modalities)
• Low rate of false negatives
• Bad
• Relatively high rate of false positives
• Year 1 true positives 11, 15 false positives
• Need for frequent repeat studies
• To increase yield need both US and mammogram
• JAMA 2921317 (2004)

13
What should you recommend to your patients?

• Difficult to ignore the large number of positives
  in multiple studies of high-risk pts, so, once
  identified, ere on side of complete screening for
  this group
• Data insufficient to recommend to broader group

14
Discussion points today

• Screening strategies, and when to start
• Role of MRI in screening
• Role of aromatase inhibitors

15
Performance of AIs is excellent

• ATAC Trial (Anastrozole). Adjuvant trial, median
  F/U 68 mos. Hazard ratio for DFS with AI 0.87
• BIG 1-98 (Letrozole). Adjuvant trial, median F/U
  26 mos. Hazard ratio for DFS with AI 0.81
• IES (Exemestane). Sequential trial, median F/U
  31 mos. Hazard ratio for DFS with AI 0.68
• MA.17 (Letrozole) Extended adjuvant trial, median
  F/U 30 mos. Hazard ratio for DFS with AI 0.58

16
Side-effects

• Gynecologic sx
• Hot flashes
• Sexual dysfunction
• Cognitive dysfunction
• Non-ischemic cardiac events
• Osteopenia/arthralgias

17
Osteopenia/arthralgias interventions

• Osteopenia
• Weight-bearing exercise
• Calcium/vitamin D
• Bisphosphonates
• (insufficient trials to determine efficacy)
• Arthralgias
• Resistance-exercise, weight loss
• May need to switch to tamoxifen

18
Side-effects less common with AIs than Tamoxifen

• Endometrial CA
• Stroke
• Thromboembolic disease

19
Unanswered questions

• Results of all cross-over arms of trials (with
  TAM and AIs)
• Duration of therapy
• Discrimination of mechanisms of resistance, and
  which pts require
• Increased estrogen blockade
• Blockade of alternate signal pathways
• Inhibition of angiogenesis