Pathology
1) microinvasive breast cancer: extends less than 1mm into basement membrane; considered subset of T1 (T1mic)
2) invasive ductal carcinoma: most common; frequently has DCIS component; extensive intraductal component is defined as more than 25% of the sample containing DCIS; if margins are negative, EIC does not predict for local recurrence
3) invasive lobular carcinoma: often mammographically silent; higher rates of being ER+ than IDC; cells are lined up in rows
4) invasive micropapillary carcinoma: rare but thought to be more aggressive
5) metaplastic carcinoma: also rare; high rates of Her-2-neu+, ER/PR-
6) metaplastic sarcomatoid carcinoma: rare, aggressive
7) spindle cell carcinoma: low metastatic potential but can recur locally
8) cystosarcoma phylloydes: despite sarcoma nomenclature can usually be excised and observed
9) medullary carcinoma: more favorable subtype; poorly differentiated appearing but encapsulated and associated with a pronounced lymphocytic infiltrate; associated with BRCA1 mutated patients
10) tubular carcinoma: also favorable histology
Prognostic factors
1) Tumor size: predicts nodal risk, OS, DFS, mets
2) Axillary nodes: the most important prognostic factor for OS and DFS across multiple trials
3) Histology: tubular, mucinous, medullary are favorable; metaplastic and undifferentiated are worse; LVSI also predicts local recurrence
4) Other pathologic poor prognostic indicators: high grade, ER/PR-, Her2+ (in node + patients), higher proliferative indices, DNA aneuploidy
5) Age: younger patients have a higher risk of local recurrence; young age is also associated with higher grade tumors which have worse survival; age may not be a prognostic factor independently of grade
6) Race: black women are at higher risk of having triple negative phenotype, tend to be higher stage at diagnosis; breast cancer has a lower overall incidence in black women in the US but a higher mortality rate
Impact of improved local control on survival
EBCTG analysis: 42,000 patients, 78 randomized controlled trials
RT showed ~5% overall survival benefit at 15 years for both mastectomy and breast conservation pts
Estimated that one death from breast cancer is prevented for every 4 local recurrences prevented by the addition of RT
Early stage invasive: contraindications for breast conservation
1) pregnancy
2) prior breast or chest RT (dose dependent)
3) active scleroderma or lupus
4) inability to resect to negative margins/multicentric disease
5) large tumor to breast ratio secondary to poor cosmetic outcomes
Trials establishing BCT as equivalent to mastectomy
1) Veronesi (Milan): mastectomy vs. quadrantectomy + axillary dissection + RT
20-yr OS: 41% 42%
20-yr LR: 2% 9%
2) NSABP B-06: mastectomy vs. lumpectomy vs. lumpectomy + RT
20-yr OS: 48% 48% 48%
20-yr IBTR: 15% 39% 14%
3) Meta-analysis (Vinh-Hung et al): 9,000 patients in 15 trials
Radiation increased local control by a factor of 3 compared with lumpectomy alone
8.6% excess mortality is observed in patients who have lumpectomy without RT
4) NSABP B-21: arms were lumpectomy + RT (LR 9%), lumpectomy + tamoxifen (LR 17%), lumpectomy + RT and tamoxifen (LR 3%) with equivalent OS across all arms
Breast conservation in older patients
1) Hughes: patients older than 70 randomized to L + tam (5Y OS 86%, DFS 96%) vs. L + tam + RT (5Y OS 87%, 5Y DFS 99%); difference in DFS was statistically significant but small in magnitude
2) Fyles: patients older than 50 randomized to L + RT + tam (5Y LC 99.4%) vs. L + tam (5Y LC 92.3%); overall survival was the same in both groups (better than 95%)
Boost vs. no boost
EORTC trial randomized patients with complete excision to 50Gy +/- 16Gy boost
-LC in boost arm was 93.8% vs. 89.8% in 50Gy alone arm
and patients with positive margins to 50Gy + 10Gy vs. 26Gy
-LC in the low dose arm was 82.5% vs. 89.2% in the high dose
Predictors of local failure: young age, not receiving boost; margins did not appear to matter
The greatest benefit to boost was seen in younger women, but all ages appeared to benefit
Extra RT did not affect survival
Hypofractionation
NCIC randomized early stage patients to 42.5Gy (16fx) vs. 50Gy (25fx)
-Identical disease control and cosmesis at 5 years
-Patients with separations greater than 25cm were excluded
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