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ACP: Breast Cancer Update. Elaine A. Muchmore, M.D. UC San Diego 10/20/07. Breast Cancer. Breast cancer affects more than 150,000 women each year, with a lifetime incidence of greater than 10%.

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Acp breast cancer update

ACP: Breast Cancer Update

Elaine A. Muchmore, M.D.

UC San Diego

10/20/07


Breast cancer
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.


Discussion points today
Discussion points today:

  • Screening strategies, and when to start

  • Role of MRI in screening

  • Role of aromatase inhibitors


Screening strategies when to start
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


What are the real issues
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.


Consensus panel recommendation
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


Should you recommend screening for women at age 40
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)


Discussion points today1
Discussion points today:

  • Screening strategies, and when to start

  • Role of MRI in screening

  • Role of aromatase inhibitors


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) 292:1317)

Breast cancer screening strategies


No free lunch costs of screening
No free lunch: costs of screening

  • 236 high-risk women examined with exam, US, mammogram, MRI (JAMA 292:1317, 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 exam+mammogram detected by MRI

  • Conclusion: all screening strategies required in high risk patients for maximum sensitivity


Costs of screening
Costs of screening

  • In another study of high-risk women (Radiology 244:381, 2007), 171 women screened with MRI+US+mammogram. Av. Age=45

  • Results:

    • 60 positives

    • 31 MRI+ only, yielding 4 CA

    • 6 MRI+, mammogram +, yielding 1 CA

    • 1 MRI+, mammogram+, US+, yielding 1 CA

    • Positives on MRI+US, only on US, mammogram+US yielded no cancers


Mri good and bad
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 292:1317 (2004)


What should you recommend to your patients
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


Discussion points today2
Discussion points today:

  • Screening strategies, and when to start

  • Role of MRI in screening

  • Role of aromatase inhibitors


Performance of ais is excellent
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


Side effects
Side-effects

  • Gynecologic sx

  • Hot flashes

  • Sexual dysfunction

  • Cognitive dysfunction

  • Non-ischemic cardiac events

  • Osteopenia/arthralgias


Osteopenia arthralgias interventions
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


Side effects less common with ais than tamoxifen
Side-effects less common with AIs than Tamoxifen

  • Endometrial CA

  • Stroke

  • Thromboembolic disease


Unanswered questions
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


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