Breast Cancer: Key issues for the non-oncologist Primary Care - - PDF document
4/7/15 Breast Cancer: Key issues for the non-oncologist Primary Care Medicine Jeffrey A. Tice, MD Associate Professor Update 2015 Department of Medicine April 2015 Department of Medicine I have no financial disclosures I
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Department of Medicine
Primary Care Medicine Update 2015
Jeffrey A. Tice, MD Associate Professor
April 2015 Department
will be discussed. I hold no patents and derive no financial benefit from the model.
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– Dr. Judith Walsh – Follow-up abnormal mammography
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ages 1 and 4. She started menstruating at age 11 and took birth control pills from age 19 to 26.
lump which was benign (cyst)
drinks 2-3 glasses of wine/night.
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cancer in U.S. women
– 1 in 8-9 women will be diagnosed in her lifetime
women
– > 40,000 deaths in 2015
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Risk factors for breast cancer
– Age – Breast density – Atypical hyperplasia – LCIS – BRCA mutation
– Family history – Breast biopsy – Race / ethnicity – Hormone therapy – Hormone levels (E2, T, IGF-1) – Benign breast disease
– Age at first birth – Menarche age – Height, weight, BMI – Bone mineral density – NAF/Lavage – SNPs – Age of diagnosis for family history – 2nd degree relatives – Alcohol intake – Diabetes – Physical activity – Breast feeding – Menopause age
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Gail et al. J Natl Cancer Inst 81:1879; 1989.
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Validated for populations; but modest discriminatory value for the individual.
Rockhill et al. J Natl Cancer Inst 93:358, 2001.
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ages 1 and 4. She started menstruating at age 11 and took birth control pills from age 19 to 26.
lump which was benign (cyst)
drinks 2-3 glasses of wine/night.
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1. < 0.5% 2. 0.5 to 1.49% 3. 1.5 to 2.49% 4. ≥ 2.5%
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1.0%
25.8% Average 35 year old woman
0.3%
12.6%
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Risk factors not in Gail model
– Age – Atypical hyperplasia – LCIS
– Family history – Breast biopsy – Race / ethnicity – Hormone levels (E2, T, IGF-1) – Benign breast disease
– Age at first birth – Menarche age – Height, weight, – Bone mineral density – NAF/Lavage – SNPs – Age of diagnosis for family history – 2nd degree relatives – Diabetes – Breast feeding – Menopause age
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RR
a Almost entirely fat 1.0 b Scattered densities 2.0 c Heterogeneously dense 2.8 d Extremely dense 4.1
Kerlikowske JNCI 2007
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radiologists must inform women
– that they have dense breasts – that dense breasts make it harder to detect breast cancer – That dense breasts are associated with a higher risk
bill is before Congress
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Tice, Annals IM, 2008.
https://tools.bcsc-scc.org/BC5yearRisk/
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Gail Model 1.0% BCSC Model
.24%
.50%
.77%
1.0% (Average 35 yo woman’s 5 year risk is 0.3%)
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single most important risk factor not included in current models
– Each individual SNP contributes little information – 76 SNPs combined are more powerful than any other risk factor
since the Supreme Court invalidated the patents
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1. Eating more fruits and vegetables 2. Brisk walking 30 minutes/day 3. Losing 10 kg (to BMI of 24 kg/m2) 4. Cutting back on alcohol
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1. Eating more fruits and vegetables 2. Brisk walking 30 minutes/day 3. Losing 10 kg (to BMI of 24 kg/m2) 4. Cutting back on alcohol
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No association with breast cancer
– Smith-Warner, JAMA, 2001 – Pooled prospective studies – 7377 cases in 351,825 women
Mixed results on dietary fat intake – the jury is still out Obesity
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10 20 30 40 50 60 Total Alcohol Intake g/d
Multivariate Relative Risk
2.5 2.0 1.5 1.0
Smith-Warner, 1998 7% increase in risk per drink per day
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decreased risk
thinner women
matters
0.2 0.4 0.6 0.8 1 1.2 ≤5 5 to 10 >40 RR MET-h/week WHI Observational Cohort (n=74,171; 1780 cancers)
McTiernan, JAMA, 2003.
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Women’s Health Initiative
1.24 (1.01-1.54) ITT 1.49 (as treated)
0.77 (0.62-0.95)
years of stopping therapy
Chlebowski,; NEJM 2009; Anderson, Lancet Onc, 2012.
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Cuzick, Lancet, 2013
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38% reduction (31-44%)
51% reduction (42-57%)
31% reduction (10-47%)
– Risk reduction years 10+ equal to years 1-10
Cuzick, Lancet, 2013: Cuzick, Lancet Onc, 2015
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1.9 (1.4-2.6)
** Majority of adverse events in women ≥ 50 years during 5 years active treat.
Fisher JNCI,1998; Cuzick Lancet, 2003; Barrett-Conner, NEJM, 2006.
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with women at increased risk of breast cancer regarding medications to reduce their risk. For women who are at increased risk for breast cancer and at low risk for adverse medication effects, clinicians should offer to prescribe risk- reducing medications such as tamoxifen or raloxifene.”
breast cancer risk of 3% or greater are more likely to benefit from tamoxifen or raloxifene”
http://www.uspreventiveservicestaskforce.org/
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– Equivalent reduction in IBC – Less thromboembolism, uterine cancer, and cataracts – Primary care comfort with therapy
– Less reduction in DCIS/LCIS: long-term follow- up concerns – Post-menopausal women only
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breast cancer and my paternal grandmother also had breast cancer
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This woman’s breast cancer risk greatly underestimated by Gail model
Breast, 44 Breast, 38 Breast, 29 Ovary, 42 Ana, 34
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cancer
same woman
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Population Risk Hereditary Risk By age 50 2% 33%-50% By age 70 7% 56%-87% By age 40 10%-20% 0.5%
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– 50% reduction in breast cancer
– 90% - 95% risk reduction Rebbeck , NEJM 2002 Kauf, NEJM 2002 Rebbeck, JNCI 1999 Rebbeck, JCO, 2004
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– 14% positive for a deleterious mutation – 32% in genes other than BRCA1 / 2
– $1500 including BRCA1/2 vs $4000 at Myriad – Genetic counseling highly recommended
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Breast Cancer Susceptibility
Low... Intermd... BRCA2 CDH1 NBN NF1 PTEN P53 STK11 CHEK2 BRCA1 High...
Hereditary breast and ovarian cancer Hereditary diffuse gastric cancer Cowden syndrome Li Fraumeni syndrome Li Fraumeni-like syndrome
FGFR2 LSP1 MAPSK1 TGFB1 TOX3
Peutz-Jegher syndrome Nijnegen breakage syndrome Neurofibromatosis 1
ATM PALB2 RAD50 BRIP1 ??? ??? ???
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after ten mammograms
Elmore et al NEJM 1998
40’s and 50’s
Nelson et al Annals Int Med 2009
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for her screening mammogram. A few days later, you get a call from the
increased density and possibly a calcification on the right. The radiologist says they are reading it as a BIRADS 0 and the patient should get follow-up, could you please let her know?
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interval
compression views
for a biopsy
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American College of Radiology BIRADS
category (breast imaging reporting and data system) Normal
1: negative routine follow-up 2: benign finding routine follow-up
Abnormal
0: indeterminate immediate follow-up (spot-compression views +- u/s) 3: low chance malignancy (~2%) short interval follow-up (3-6 months repeat mammo) 4: >2-95% chance malignancy (a: low; b: intermediate; c: moderate) biopsy 5: ≥95% chance invasive malignancy biopsy
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report of her mammogram within 30 days of exam
understand
contact patient as soon as possible – ‘expectation’ within 5 days
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www.fda.gov/Radiation-EmittingProducts/ MammographyQualityStandardsActandProgram/ConsumerInformation/ucm113968.htm
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results improves receipt of appropriate follow-up
Poon et al, JGIM 2004
adequate communication, and are less likely to know their abnormal mammogram results
Zapka et al, Prev Med 2004
(in person or over the telephone) more likely to know that their mammogram was abnormal
Karliner et al, JGIM 2005
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diagnosis experience delays to diagnosis or treatment
associated with 12% lower 5-year survival – Most of this attributable to later stage disease
Richards et al, Lancet 1999
suffer delays than White women
Elmore et al, Med Care 2005
English speaking and minority women have longer delays
Karliner et al, Med Care 2011
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Chinese-American woman, for her routine annual exam. She tells you about a new lump she found in her breast, which you feel and find to be firm with regular borders.
mammogram which shows an area of calcification BIRADS 4 and next she undergoes a core biopsy.
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1. ER/PR positive staining 2. ER/PR and HER2Neu positive staining 3. ER/PR/Her2Neu negative staining
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Assay for estrogen, progesterone receptors and HER2
– Perform on core biopsy specimen – If negative on core specimen, should be repeated at definitive surgery:
specimen will be positive on larger surgical specimen
estrogen therapy
– worse prognosis – responsive to trastuzumab (Herceptin)
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– ER- / PR- / HER2- – Unresponsive to anti-estrogen therapy and trastuzumab – Neo-adjuvant chemotherapy – Clinical trials investigating immune modulators and receptor-blockers for growth factors
carriers more at risk for triple negative tumors
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palpable nodes
from the primary tumor (can be >1)
dye injection around tumor / biopsy cavity / subareolar
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years of follow-up; largest of 10 RCTs
ALND in +SLN only ALND in all Overall Survival 90.3% 91.8% Disease Free Survival 81.5% 82.4%
If SLN negative: no axillary dissection!
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Krag et al, Lancet Oncology 2010
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– RCT of no further axillary treatment vs. ALND
– T1-T2 invasive breast cancer, no palpable adenopathy,
– No difference in 5-year overall or disease free survival – Only able to enroll half target (891/1900 women) No ALND ALND Overall Survival 92.5% 91.8% Disease Free Survival 83.9% 82.2%
Giuliano et al, JAMA 2011
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risk
668 ER+ LN- patients treated with tamoxifen Risk group % of sample 10-year recurrence Low 51% 6.8% Intermediate 22% 14.3% High 27% 30.5%
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Paik 2004
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Recurrence Score Group Tam 10-year DRR Tam+CRX 10-year DRR RR (95% CI) Low risk (<18) 3.2 4.4 1.31 (0.46-3.78) Intermediate risk (18-30) 9.1 10.9 0.61 (0.24-1.59) High risk (>30) 29.5 11.9 0.26 (0.13-0.53)
Tam = Tamoxifen; CRX = chemotherapy; DRR = distant recurrence rate, RR = relative risk Table: Effect of chemotherapy on ten-year distant recurrence rates (Paik JCO 2006) Ongoing RCTs using Oncotype Dx (TAILORx) and Mammaprint (MINDACT)
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Risk Reduction
– Exercise, weight loss or maintenance – Minimize alcohol – Avoid/stop HT – Low fat diet?
risk women
– Refer to genetic counseling / high risk breast clinic
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Tests at Diagnosis
abnormal mammogram
improves receipt of appropriate follow-up
and results can help determine need for chemo
for chemotherapy by 50% in women with ER+, LN- disease