Chemotherapy is more effective in patients with breast cancer not expressing steroid hormone receptors: a study of preoperative treatment.
OBJECTIVE
The purpose of this research was to identify factors predicting response to preoperative chemotherapy.


METHODS
In a large volume laboratory using standard immunohistochemical methods, we reviewed the pretreatment biopsies and histologic specimens at final surgery of 399 patients with large or locally advanced breast cancer (cT2-T4, N0-2, M0) who were treated with preoperative chemotherapy. The incidence of pathological complete remission and the incidence of node-negative status at final surgery were assessed with respect to initial pathological and clinical findings. Menopausal status, estrogen receptor status, progesterone receptor status [absent (0% of the cells positive) versus expressed], clinical tumor size, histologic grade, Ki-67, Her-2/neu expression, and type and route of chemotherapy were considered.


RESULTS
High rates of pathological complete remission were associated with absence of estrogen receptor and progesterone receptor expression (P < 0.0001), and grade 3 (P = 0.001). Significant predictors of node-negative status at surgery were absence of estrogen receptor and progesterone receptor expression (P < 0.0001), clinical tumor size <5 cm (P < 0.001), and use of infusional regimens (P = 0.003). The chance of obtaining pathological complete remission or node-negative status for patients with endocrine nonresponsive tumors compared with those having some estrogen receptor or progesterone receptor expression was 4.22 (95% confidence interval, 2.20-8.09, 33.3% versus 7.5%) and 3.47 (95% confidence interval, 2.09-5.76, 42.9% versus 21.7%), respectively. Despite the significantly higher incidence of pathological complete remission and node-negative status achieved by preoperative chemotherapy for patients with estrogen receptor and progesterone receptor absent disease, the disease-free survival was significantly worse for this cohort compared with the low/positive expression cohort (4-year disease-free survival %: 41% versus 74%; hazard ratio 3.22; 95% confidence interval, 2.28-4.54; P < 0.0001).


CONCLUSIONS
Response to preoperative chemotherapy is significantly higher for patients with endocrine nonresponsive tumors. New chemotherapy regimens or combinations should be explored in this cohort of patients with poor outcome. For patients with endocrine responsive disease, the role of preoperative endocrine therapies should be studied.
Colleoni
Marco
M
Department of Medicine, European Institute of Oncology, Milan, Italy. marco.colleoni@ieo.it
Viale
Giuseppe
G
Zahrieh
David
D
Pruneri
Giancarlo
G
Gentilini
Oreste
O
Veronesi
Paolo
P
Gelber
Richard D
RD
Curigliano
Giuseppe
G
Torrisi
Rosalba
R
Luini
Alberto
A
Intra
Mattia
M
Galimberti
Viviana
V
Renne
Giuseppe
G
Nolè
Franco
F
Peruzzotti
Giulia
G
Goldhirsch
Aron
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D016019:Survival Analysis; D016896:Treatment Outcome
D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone