Breast Studies

BREAST CONSERVATION (BCT)

NSABP B06 Fisher, NEJM 2002

  • 1843 women with < 4 cm tumor.
ARMS MASTECTOMY LUMPECTOMY LUMP + 50 GY p-value
Recurrence: in breast 10% 39% 14% < 0.01
OS 47% 46% 46% N.S.

EBCTCG Meta-analysis– Lancet 2005.

ARMS BCS BCS + RT
Isolated local recurrence at 5-yrs 25.9% 7.3%
.. Node-negative 22.9% 3.7%
.. Node-positive 41.1% 11.0%
Breast cancer mortality at 15-yrs 35.9% 30.5%
Non breast-cancer mortality at 15-yrs 14.6% 15.9%

4-to-1 ratio of absolute effects (ie. 20% reduction in 5-yr local recurrence leads to 5% reduction in 15-yr breast cancer mortality).

MORE BCT TRIALS

DUCTAL CARCINOMA IN-SITU (DCIS)

NSABP B06

(J Surg Oncol. 1991 Jul;47(3):139-47)

  • 78 women had DCIS (incidentally) instead of invasive cancer on central review
ARMS MASTECTOMY LUMPECTOMY LUMP + 50 GY
Recurrence at 83 mo. 0% 43% 7%

NSABP B17

(Fisher, 1998 JCO 16(2):441-452)

8-years BCS BCS + 50 Gy p-value
Ipsilateral recurrence rate 26.8% 12.1% Sig
.. Invasive 13.4% 3.9% Sig
.. Non-invasive 13.4% 8.2% Sig
Contralatateral breast tumor rate 3.3% 5.7% Not sig

NSABP B24

(Fisher, 1999 Lancet 353;1993)

  • 1804 women with DCIS
6 -years BCS + 50 Gy BCS + 50 Gy + TAM
Ipsilateral recurrence rate 19.6 % 13.75 %
.. Invasive 8.73% 5.02%
.. Non-invasive 10.6 % 9.02 %

Princess Margret Hospital (TAM +/- RT)

(N Engl J Med. 2004 Sep 2;351(10):963-70)

  • Women age > 50 years, Invasive Breast cancer < 5 cm, ER/PR positive or negative
5-yrs BCS + TAM + 50 Gy BCS + TAM p-value
local relapse 0.6 % 7.7% < 0.01
axillary relapse 0.5% 2.5% .05
DFS 91% 84% < 0.01
< 2 cm tumor subgroup analysis
local relapse 0.4 % 5.9% < 0.01

POST-MASTECTOMY RADIATION THERAPY (PMRT)

British Columbia Danish 82b Danish 82c
Patient Characteristics 318 pre-menopausal women,
• 1978-1986,
• LN(+) only
1706 pre-menopausal women,
• > 5 cm,
• LN(+),
• skin/CW invasion.
• Only 8% node negative.
1460 Post-menopausal women,
• > 5 cm,
• LN(+),
• skin/CW invasion.
• Only 8% node negative.
Arms 1. CMF
2. CMF + RT
1. CMF
2. CMF + RT
3. CMF + tamoxifen
1. TAM
2. TAM + RT,
3. TAM + CMF
Chemotherapy same 82b, Given for 12 months through 1981, 6 months after 1981 CMF:
cyclophosphamide 600mg/m2;
methotrexate 40mg/m2
fluorouracil 600mg/m2
total of 8-9 cycles, held during RT
CMF same as 82b
Hormonal Therapy Tamoxifen 30 mg QD x 1 year
Surgery MRM + level I+II axillary dissection.
Median 11 nodes
total mastectomy and axillary dissection including level I and part of level II.
Median of 7 nodes
Radiation Co-60 for all fields
• 37.5 Gy/16 fx to chest wall
• 35 Gy to supraclav / axilla (SC+PAB fields) and IMC
50 Gy/25 fx or 48 Gy/22 fx,
• Medial chest wall (electrons),
• supraclav /axillary/lat chest wall(photons),
• IMC nodes (electrons; 1st-4th IC spaces)
Time course of CT and RT “Sandwich” RT Given between 5th and 6th cycle of chemo “Sandwich” RT after 1st cycle of CMF: 50 Gy/25 fx or 48 Gy/22 fractions
Results
LRF with S + Systemic 26% 32% 35%
LRF with addition of RT 10% 9% 8%
Other Results • OS-20 (37 vs. 47%) (p=0.03). (NS at 15-yr FU)
• Benefit RT same for 1-3 nodes vs 4+ nodes pts.
• 1/3 of Breast Cancer events and deaths reduced by RT
• OS-10 54% vs 45% p < 0.001
• OS benefit more prominent in 1-3 nodes positive subgroup
• concurrent CT + TAM has higher mortality
• Overall Survival 45% vs 36% < 0.001.
• OS benefit extends to 1-3 LN positive subgroup analysis.

Additional points from British Columbia and Danish trials:

  • Danish

1. No increase in non-breast cancer mortality using electron to tx the chest wall.
2. Prognostic factors include tumor size, number of (+)nodes, grade, and RT
3. Problems include

  • low number of nodes dissected (but British Columbia had 11 nodes)
  • high relapse rate of > 30% in the control arms
  • high % of axillary failures,
  • low dose chem.

4. Tamoxifen should not be taken during chemo.

  • British Columbia Study

1. Complications:
2. arm edema 10%, only 4% moderate-severe
3. Pneumonitis 0.6%
4. No brachial plexopathy
5. No increase in second cancers (8%)
6. Also, 6 months of CMF gives same results as 12 months

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