Transcript Biologic Differences in Postmenopausal Women

Breast Cancer in Elderly (>65 Years)
Recommendations of the International
Society of Geriatric Oncology

Surgical recommendations are similar to those in younger patients

Radiotherapy
– Considered after breast conservation therapy, taking into account patient
health, functional status, and local recurrence risk

Unlikely to affect overall survival
– Postmastectomy if 4+ lymph nodes or T3–4


May be omitted if life expectancy <5 years and low risk of locoregional recurrence
Adjuvant systemic therapy
– Tamoxifen and/or aromatase inhibitor (AI) appropriate for hormone-sensitive
tumors

Consider toxicity profiles and slightly higher efficacy of AI
– Chemotherapy choices should take into account absolute benefit, life
expectancy, and tolerability

Treatment goals for metastatic disease are similar to those in younger
patients
Wildiers H, et al. Lancet Oncol. 2007;8:1101.
Age and Molecular Subtypes
Basal-like
(P < .0001)
HER2
Positive/
ER
Negative
Luminal Luminal Unclass
A
B
-ified
Premenopause
55%
40%
41%
47%
53%
Postmenopause
45%
60%
59%
53%
47%
Millikan RC, et al. Breast Cancer Res Treat. Epub ahead of print.
Quantative ER and Age
Tamoxifen-Treated Arms B-14 and B-20
ER (fmol/mg) Median
120
P <.0001
105
100
44–231
80
70
30–132
60
40
37
21–69
20
0
≤40
1
50–59
2
Age (years)
≥60
3
Quantative ER and Therapeutic Efficacy
NSABP Studies
B–14
B–20
100%
90%
Event-Free at 12 y Postsurgery
90%
80%
70%
82%
78%
69%
88%
82%
76%
Placebo
68%
Tamoxifen
CMFT
60%
50%
40%
30%
20%
10%
0%
10–49
1
≥50
2
10–49
3
ER (fmol/mg) Median
≥50
4
Chemotherapy Toxicity by Age
6174 patients treated in 3 chemotherapy trials
• CALGB 8541: CAF at varying schedules and doses
• CALGB 9344: AC at varying doses, with or without paclitaxel
• CALGB 9741: Dose-dense vs standard AC-paclitaxel
≤50 Years
(n = 3393)
51–64 Years
(n = 2323)
>65 Years
(n = 458)
WBC (grade 4; P < .0001)
16%
17%
17%
Platelets (grade 4)
3%
4%
4%
Hemoglobin (grade 4)
1%
1%
1%
Nausea/vomiting (grade 3–4)
10%
7%
7%
Diarrhea (grade 3–4)
1%
2%
1%
Stomatitis (grade 3–4)
5%
4%
5%
Neurologic (grade 3–4)
8%
9%
9%
Muss HB, et al. J Clin Oncol. 2007;25:3699.
Clinicopathologic Differences in
Breast Cancer in Older Women

Histology1,2
– Increased mucinous, lobular
– Decreased medullary

Favorable biologic characteristics
– Endocrine responsive2
– Fewer p53 mutants2
– Lower proliferative indices2
– Fewer basal-like and more luminal A3
1. Li C, et al. Cancer Epidemiol Biomarkers Prev. 2006;15:946. 2. Diab S, et al. J Natl Cancer Inst.
2000;92:550. 3. Millikan RC, et al. Breast Cancer Res Treat. Epub ahead of print.
Carcinogenesis
• High ER
• Differentiated
• Luminal
markers
• Induced by
HRT
• Sensitive to
endocrine
therapy
Dontu G, et al. Trends Endocrinol Metab. 2004;15:193.
Breast Cancer in African-American
Women

Lower overall risk, but recent decrease in incidence not seen in
African Americans
– Annual percentage change (1999–2004)

Caucasians: 2.9%

African Americans: 0.5%1

Less likely to receive adequate mammography and more likely to
have higher stage at diagnosis2

Differences in molecular subtypes
– Higher prevalence of basal-like
– Lower prevalence of luminal A3

Worse survival, partly due to differences in screening, tumor
characteristics, and treatment4
1. Li C, et al, Cancer Epidemiol Biomarkers Prev. 2007;16:2773. 2. Smith-Bindman R, et al.
Ann Intern Med. 2006;144:541. 3.Carey LA, et al. JAMA. 2006;295:2492. 4. Curtis E, et al. Cancer.
2008;112:171-180.