Immunohistochemical surrogate markers of breast cancer molecular classes predicts response to neoadjuvant chemotherapy: a single institutional experience with 359 cases.
BACKGROUND
Complete pathologic response to neoadjuvant chemotherapy (NACT) is predominantly seen in "ERBB2" and "basal-like" tumors using expression profiling. We hypothesize that a similar response could be predicted using semiquantitative immunohistochemistry for estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2).


METHODS
ER, PR, and HER2 were used to classify 359 tumors treated with NACT into 6 groups: luminal A (strong ER+, HER2 negative), luminal B (weak to moderate ER+, HER2 negative), triple negative (negative for ER, PR, and HER2), ERBB2 (negative for ER and PR, but HER2+), luminal A-HER2 hybrid (strong ER+ and HER2+), and luminal B-HER2 hybrid (weak to moderate ER+ and HER2+). Complete pathologic response was defined as absence of invasive carcinoma in the breast and regional lymph nodes.


RESULTS
Thirteen percent (48 of 359) demonstrated complete pathologic response. The highest rate of complete pathologic response was seen in ERBB2 (33%; 19 of 57) and triple negative (30%; 24 of 79) tumor classes. Among the ER+ "molecular" group, the highest rate of complete pathologic response was seen among luminal B-HER2 hybrid tumors, 8% (2 of 24). Remainder of ER+ tumors demonstrated a very low rate of complete pathologic response, 1.5% (3 of 198). The 5-year survival for patients achieving complete pathologic response was 96% compared with 75% in patients that failed to achieve complete pathologic response. The overall survival was worse in the ER-negative group (ERBB2 and triple negative) compared with the ER-positive group.


CONCLUSIONS
We confirm the recently defined "triple negative paradox," or rather "hormone receptor negative paradox," that despite the best response to NACT, ERBB2 and triple negative tumors show the worst overall survival because of higher relapse among those with residual disease.
Department of Pathology, Magee-Womens Hospital of UPMC, 300 Halket Street, Pittsburgh, PA 15213, USA. rbhargava@mail.magee.edu
Rohit
R
Bhargava
Sushil
S
Beriwal
David J
DJ
Dabbs
Umut
U
Ozbek
Atilla
A
Soran
Ronald R
RR
Johnson
Adam M
AM
Brufsky
Barry C
BC
Lembersky
Gretchen M
GM
Ahrendt
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human