2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

BIOLOGY AND LOCAL THERAPY DECISIONS
mitigate this risk through routine use of chemotherapy,
achievement of negative surgical margin status, and use of
a tumor bed boost. Patients with triple-negative disease
should not be routinely recommended to undergo mastectomy.
A recent study from Edmonton, Canada, evaluated
768 patients with T1–2N0 triple-negative disease and found
better 5-year local-regional recurrence-free survival after
BCT with radiation compared with mastectomy without
radiation (96% compared with 90%, respectively, p � 0.027;
hazard ratio, 2.53; p � 0.0264). 9
Mastectomy with or without Radiation
Biologic subtypes also appear to affect the risk of localregional
recurrence after mastectomy. For example, a British
Columbia study that combined data from patients
treated with mastectomy alone and patients treated with
mastectomy plus radiation demonstrated that luminal A
subtype independently correlated with a lower risk of localregional
recurrence after mastectomy compared with the
other subtypes. 4 Interestingly, in an analysis of patients
KEY POINTS
● Estrogen receptor (ER)-positive, HER2/neu-negative
breast cancers have very low local-regional recurrence
rates after adjuvant radiation treatments.
● Triple-negative breast cancer has higher rates of
local-regional recurrence after adjuvant radiation
compared with similar stages of ER-positive disease.
● Breast-conservative therapy remains an appropriate
treatment option for patients with early-stage, triplenegative
disease.
Author’s Disclosure of Potential Conflicts of Interest
Author
Thomas A. Buchholz*
*No relevant relationships to disclose.
Employment or
Leadership
Positions
Consultant or
Advisory Role
1. Cabioglu N, Hunt KK, Buchholz TA, et al. Improving local control with
breast-conserving therapy: A 27-year single-institution experience. Cancer.
2005;104:20-29.
2. Nguyen PL, Taghian AG, Katz MS, et al. Breast cancer subtype approximated
by estrogen receptor, progesterone receptor, and HER-2 is associated
with local and distant recurrence after breast-conserving therapy. J Clin
Oncol. 2008;26:2373-2378.
3. Albert JM, Gonzalez-Angulo AM, Guray M, et al. Estrogen/progesterone
receptor negativity and HER2 positivity predict locoregional recurrence in
patients with T1a,bN0 breast cancer. Int J Radiat Oncol Biol Phys. 2010;77:
1296-1302.
4. Voduc KD, Cheang MC, Tyldesley S, et al. Breast cancer subtypes and
the risk of local and regional relapse. J Clin Oncol. 2010;28:1684-1691.
5. Nuyten DS, Kreike B, Hart AA, et al. Predicting a local recurrence after
breast-conserving therapy by gene expression profiling. Breast Cancer Res.
2006;8:R62.
6. Mamounas EP, Tang G, Fisher B, et al. Association between the 21-gene
recurrence score assay and risk of locoregional recurrence in node-negative,
estrogen receptor-positive breast cancer: Results from NSABP B-14 and
NSABP B-20. J Clin Oncol. 2010;28:1677-1683.
7. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant
treated on the Danish postmastectomy radiation trials and
those who were randomly selected to not receive radiation,
the risks of local-regional recurrence for patients with ERpositive
disease and those with ER-negative disease was
similar (34% and 31%, respectively). 10 However, in the
patients randomly selected to receive postmastectomy radiation,
the rates of local-regional recurrence were lower in
the patients with ER-positive disease compared with those
with ER-negative disease (4% and 14%, respectively). 10
Similarly, a report of local-regional treatment outcome of
patients treated at MDACC with mastectomy, no radiation,
and adjuvant chemotherapy did not find ER status to independently
correlate with local-regional recurrence (15% ER
positive and 12% ER negative). 11 However, in a recursive
partition analysis of patients treated with postmastectomy
radiation, ER-negative disease proved to be the most powerful
discriminator of local-regional recurrence risk. 12
Radiation Resistance and Future Research
Collectively, the data from breast conservation and postmastectomy
radiation raise the hypothesis that ER negativity
or triple-negative disease may be a more radiationresistant
histology than ER-positive disease. These data
were also supported by the most recent update of the Early
Breast Cancer Trialists’ Group meta-analysis of trials
comparing use with omission of radiation after breastconservation
surgery. In these trials, the proportional reduction
in the risk of recurrence with radiation was nearly
60% for ER-positive disease treated with tamoxifen, approximately
50% for ER-positive disease without tamoxifen
treatment, and only 35% for ER-negative disease. These
data indicate that additional research is needed to identify
potential molecular targets in triple-negative disease and to
design new therapeutic strategies to enhance radiation
effects in this subtype.
Stock
Ownership Honoraria
REFERENCES
Research
Funding
Expert
Testimony
Other
Remuneration
chemotherapy for operable HER2-positive breast cancer. N Engl J Med.
2005;353:1673-1684.
8. Kiess AP, McArthur HL, Mahoney K, et al. Adjuvant trastuzumab
reduces locoregional recurrence in women who receive breast-conservation
therapy for lymph node-negative, human epidermal growth factor receptor
2-positive breast cancer. Cancer. Epub 2011 Sep 1.
9. Abdulkarim BS, Cuartero J, Hanson J, et al. Increased risk of locoregional
recurrence for women with T1-2N0 triple-negative breast cancer
treated with modified radical mastectomy without adjuvant radiation therapy
compared with breast-conserving therapy. J Clin Oncol. 2011;29:2852-2858.
10. Kyndi M, Sorensen FB, Knudsen H, et al. Estrogen receptor, progesterone
receptor, HER-2, and response to postmastectomy radiotherapy in
high-risk breast cancer: The Danish Breast Cancer Cooperative Group. J Clin
Oncol. 2008;26:1419-1426.
11. Katz A, Strom EA, Buchholz TA, et al. Loco-regional recurrence
patterns following mastectomy and doxorubicin-based chemotherapy: Implications
for postoperative irradiation. J Clin Oncol. 2000;18:2817-2827.
12. Woodward WA, Strom EA, Tucker SL, et al. Locoregional recurrence
after doxorubicin-based chemotherapy and postmastectomy: Implications for
breast cancer patients with early-stage disease and predictors for recurrence
after postmastectomy radiation. Int J Radiat Oncol Biol Phys. 2003;57:336-344.
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