NcXHF

IMMUNITY IN TRIPLE-NEGATIVE BREAST CANCER
to modify the tumor immune environment to improve
prognosis for tumors that do not contain TIL. For TNBC,
controlling tumor growth with immunologically active conventional
chemotherapies in combination with immune
checkpoint inhibitors could increase response rates. For patients
with limited T-cell infıltration vaccine priming before
or concurrent with immune checkpoint inhibitors may result
in clinical benefıt. A better understanding of the immune microenvironment
and why certain subtypes of breast cancer
are more, or less, immunogenic will speed the clinical application
of immune modulatory therapies to the benefıt
of all patients with breast cancer. Lessons learned in triplenegative
disease is a great start to improved outcomes for
all.
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: None. Stock or Other Ownership Interests: Mary L. Disis, Epithany, VentiRx. Honoraria: None. Consulting or
Advisory Role: Mary L. Disis, Celgene, EMD Seronon, Emergent BioSolutions, VentiRx. Speakers’ Bureau: None. Research Funding: Mary L. Disis, Seattle
Genetics, Ventrx. Patents, Royalties, or Other Intellectual Property: Mary L. Disis, I am an inventor on patents held by the University of Washington.
Expert Testimony: None. Travel, Accommodations, Expenses: None. Other Relationships: None.
References
1. Denkert C, Loibl S, Noske A, et al. Tumor-associated lymphocytes as an
independent predictor of response to neoadjuvant chemotherapy in
breast cancer. J Clin Oncol. 2010;28:105-113.
2. Loi S, Sirtaine N, Piette F, et al. Prognostic and predictive value of
tumor-infıltrating lymphocytes in a phase III randomized adjuvant
breast cancer trial in node-positive breast cancer comparing the addition
of docetaxel to doxorubicin with doxorubicin-based chemotherapy:
BIG 02-98. J Clin Oncol. 2013;31:860-867.
3. Issa-Nummer Y, Darb-Esfahani S, Loibl S, et al. Prospective validation
of immunological infıltrate for prediction of response to neoadjuvant
chemotherapy in HER2-negative breast cancer-a substudy of the neoadjuvant
GeparQuinto trial. PLoS One. 2013;8:e79775.
4. Pedroza-Gonzalez A, Xu K, Wu TC, et al. Thymic stromal lymphopoietin
fosters human breast tumor growth by promoting type 2 inflammation.
J Exp Med. 2011;208:479-490.
5. Cecil DL, Holt GE, Park KH, et al. Elimination of IL-10-inducing
T-helper epitopes from an IGFBP-2 vaccine ensures potent antitumor
activity. Cancer Res. 2014;74:2710-2718.
6. Wimberly H, Brown JR, Schalper KA, et al. PD-L1 expression correlates
with tumor-infıltrating lymphocytes and response to neoadjuvant
chemotherapy in breast cancer. Cancer Immunol Res. Epub
2014 December 19.
7. Arnould L, Gelly M, Penault-Llorca F, et al. Trastuzumab-based treatment
of HER2-positive breast cancer: an antibody-dependent cellular
cytotoxicity mechanism? Br J Cancer. 2006;94:259-267.
8. Dieci MV, Criscitiello C, Goubar A, et al. Prognostic value of tumorinfıltrating
lymphocytes on residual disease after primary chemotherapy
for triple-negative breast cancer: a retrospective multicenter study.
Ann Oncol. 2014;25:611-618.
9. Ono M, Tsuda H, Shimizu C, et al. Tumor-infıltrating lymphocytes are
correlated with response to neoadjuvant chemotherapy in triplenegative
breast cancer. Breast Cancer Res Treat. 2012;132:793-805.
10. Ibrahim EM, Al-Foheidi ME, Al-Mansour MM, et al. The prognostic
value of tumor-infıltrating lymphocytes in triple-negative breast cancer:
a meta-analysis. Breast Cancer Res Treat. 2014;148:467-476.
11. Mao Y, Qu Q, Zhang Y, et al. The value of tumor infıltrating lymphocytes
(TILs) for predicting response to neoadjuvant chemotherapy in
breast cancer: a systematic review and meta-analysis. PLoS One. 2014;9:
e115103.
12. Mahmoud SM, Paish EC, Powe DG, et al. Tumor-infıltrating CD8
lymphocytes predict clinical outcome in breast cancer. J Clin Oncol.
2011;29:1949-1955.
13. Miyashita M, Sasano H, Tamaki K, et al. Tumor-infıltrating CD8 and
FOXP3 lymphocytes in triple-negative breast cancer: its correlation
with pathological complete response to neoadjuvant chemotherapy.
Breast Cancer Res Treat. 2014;148:525-534.
14. Baker K, Lachapelle J, Zlobec I, et al. Prognostic signifıcance of CD8 T
lymphocytes in breast cancer depends upon both oestrogen receptor
status and histological grade. Histopathology. 2011;58:1107-1116.
15. Liu S, Lachapelle J, Leung S, et al. CD8 lymphocyte infıltration is an
independent favorable prognostic indicator in basal-like breast cancer.
Breast Cancer Res. 2012;14:R48.
16. Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response
to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371:2189-2199.
17. Smid M, Hoes M, Sieuwerts AM, et al. Patterns and incidence of chromosomal
instability and their prognostic relevance in breast cancer subtypes.
Breast Cancer Res Treat. 2011;128:23-30.
18. Shah SP, Roth A, Goya R, et al. The clonal and mutational evolution
spectrum of primary triple-negative breast cancers. Nature. 2012;486:
395-399.
19. DeNardo DG, Andreu P, Coussens LM. Interactions between lymphocytes
and myeloid cells regulate pro- versus anti-tumor immunity. Cancer
Metastasis Rev. 2010;29:309-316.
20. Ferris RL, Jaffee EM, Ferrone S. Tumor antigen-targeted, monoclonal
antibody-based immunotherapy: clinical response, cellular immunity,
and immunoescape. J Clin Oncol. 2010;28:4390-4399.
21. Rody A, Karn T, Liedtke C, et al. A clinically relevant gene signature in triple
negative and basal-like breast cancer. Breast Cancer Res. 2011;13:R97.
22. Karn T, Pusztai L, Holtrich U, et al. Homogeneous datasets of triple
negative breast cancers enable the identifıcation of novel prognostic and
predictive signatures. PLoS One. 2011;6:e28403.
23. Iglesia MD, Vincent BG, Parker JS, et al. Prognostic B-cell signatures
using mRNA-seq in patients with subtype-specifıc breast and ovarian
cancer. Clin Cancer Res. 2014;20:3818-3829.
asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK
e29