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Journal of Cancer Research and Clinical Oncology

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01-05-2008 | Original Paper

Low nuclear grade but not cell proliferation predictive of pathological complete response to docetaxel in human breast cancers

Authors: Yasuo Miyoshi, Masafumi Kurosumi, Junichi Kurebayashi, Nariaki Matsuura, Masato Takahashi, Eriko Tokunaga, Chiyomi Egawa, Norikazu Masuda, Seung Jin Kim, Masatsugu Okishiro, Tetsu Yanagisawa, Satsuki Ueda, Tetsuya Taguchi, Yasuhiro Tamaki, Shinzaburo Noguchi, The Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society

Published in: Journal of Cancer Research and Clinical Oncology | Issue 5/2008

Abstract

Purpose

Predictive factors for response to docetaxel in human breast cancers have yet to be identified. The aim of the present study was to investigate the relationship of various clinicopathological and biological parameters with pathological response to docetaxel in the neoadjuvant setting.

Methods

The study population comprised 78 patients with primary breast cancers who were treated with docetaxel [60 mg/m²; four (median) cycles, range 3–6; q3w] as neoadjuvant therapy and subsequently treated with mastectomy or breast conserving surgery. Tumor samples obtained before chemotherapy were subjected to histological examination and immunohistochemistry of HER-2 and Ki-67.

Results

The pathological complete response (pCR) rate was significantly (P = 0.04) higher for tumors with low nuclear grade (NG-I or -II) (21%) than for tumors with high NG (NG-III) (5%). The pCR rate (20%) of small (≤5 cm) tumors was marginally significantly (P = 0.05) higher than that of large (>5 cm) tumors (5%). Combined analysis of NG and tumor size showed that low-NG small tumors have a higher response rate (30%) than high-NG small tumors (11%; P = 0.13), low-NG large tumors (11%; P = 0.15), and high-NG large tumors (0%; P = 0.009). No statistically significant association was observed between pCR rate and menopausal status, lymph node status, ER, PR, HER-2, or Ki-67.

Conclusions

Low nuclear grade, but not cell proliferation determined by Ki-67, is associated with a good pathological response to docetaxel. Combination of low nuclear grade and small tumor size may be useful for the selection of breast tumors with a high pCR rate (30%).

Amat S, Bougnoux P, Penault-Llorca F, Fetissof F, Cure H, Kwiatkowski F, Achard JL, Body G, Dauplat J, Chollet P (2003) Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate. Br J Cancer 88:1339–1345PubMedCrossRef

Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N, National Surgical Adjuvant Breast, Bowel Project Protocol B-27 (2003) The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 21:4165–4174PubMedCrossRef

Bottini A, Berruti A, Bersiga A, Brizzi MP, Brunelli A, Gorzegno G, DiMarco B, Aguggini S, Bolsi G, Cirillo F, Filippini L, Betri E, Bertoli G, Alquati P, Dogliotti L (2000) p53 but not bcl-2 immunostaining is predictive of poor clinical complete response to primary chemotherapy in breast cancer patients. Clin Cancer Res 6:2751–2758PubMed

Burcombe RJ, Makris A, Richman PI, Daley FM, Noble S, Pittam M, Wright D, Allen SA, Dove J, Wilson GD (2005) Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer. Br J Cancer 92:147–155PubMedCrossRef

Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Gutierrez MC, Elledge R, Mohsin S, Osborne CK, Chamness GC, Allred DC, O’Connell P (2003) Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet 362:362–369PubMedCrossRef

Di Leo A, Chan S, Paesmans M, Friedrichs K, Pinter T, Cocquyt V, Murray E, Bodrogi I, Walpole E, Lesperance B, Korec S, Crown J, Simmonds P, Von Minckwitz G, Leroy JY, Durbecq V, Isola J, Aapro M, Piccart MJ, Larsimont D (2004) HER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel. Breast Cancer Res Treat 86:197–206PubMedCrossRef

Diaz JF, Andreu JM (1993) Assembly of purified GDP-tubulin into microtubules induced by taxol and taxotere: reversibility, ligand stoichiometry, and competition. Biochemistry 32:2747–2755PubMedCrossRef

Estevez LG, Cuevas JM, Anton A, Florian J, Lopez-Vega JM, Velasco A, Lobo F, Herrero A, Fortes J (2003) Weekly docetaxel as neoadjuvant chemotherapy for stage II and III breast cancer: efficacy and correlation with biological markers in a phase II, multicenter study. Clin Cancer Res 9:686–692PubMed

Fernandez-Sanchez M, Gamboa-Dominguez A, Uribe N, Garcia-Ulloa AC, Flores-Estrada D, Candelaria M, Arrieta (2006) Clinical and pathological predictors of the response to neoadjuvant anthracycline chemotherapy in locally advanced breast cancer. Med Oncol 23:171–183PubMedCrossRef

Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672–2685PubMed

Fraizer GC, Diaz MF, Lee IL, Grossman HB, Sen S (2004) Aurora-A/STK15/BTAK enhances chromosomal instability in bladder cancer cells. Int J Oncol 25:1631–1639PubMed

Garcia P, Braguer D, Carles G, el Khyari S, Barra Y, de Ines C, Barasoain I, Briand C (1994) Comparative effects of taxol and Taxotere on two different human carcinoma cell lines. Cancer Chemother Pharmacol 34:335–343PubMedCrossRef

Hasegawa S, Miyoshi Y, Egawa C, Ishitobi M, Taguchi T, Tamaki Y, Monden M, Noguchi S (2003) Prediction of response to docetaxel by quantitative analysis of class I and III beta-tubulin isotype mRNA expression in human breast cancers. Clin Cancer Res 9:2992–2997PubMed

Hata T, Furukawa T, Sunamura M, Egawa S, Motoi F, Ohmura N, Marumoto T, Saya H, Horii A (2005) RNA interference targeting aurora kinase a suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells. Cancer Res 65:2899–2905PubMedCrossRef

Hu W, Kavanagh JJ, Deaver M, Johnston DA, Freedman RS, Verschraegen CF, Sen S (2005) Frequent overexpression of STK15/Aurora-A/BTAK and chromosomal instability in tumorigenic cell cultures derived from human ovarian cancer. Oncol Res 15:49–57PubMed

Inaji H, Kobayashi K (2005) The Journal of the Japanese Breast Cancer Society: Ggeneral rules for clinical and pathological recording of breast cancer. Breast Cancer Suppl 12:S9

Iwao-Koizumi K, Matoba R, Ueno N, Kim SJ, Ando A, Miyoshi Y, Maeda E, Noguchi S, Kato K (2005) Prediction of docetaxel response in human breast cancer by gene expression profiling. J Clin Oncol 23:422–431PubMedCrossRef

Jeng YM, Peng SY, Lin CY, Hsu HC (2004) Overexpression and amplification of Aurora-A in hepatocellular carcinoma. Clin Cancer Res 10:2065–2071PubMedCrossRef

Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, Theriault RL, Singh G, Binkley SM, Sneige N, Buchholz TA, Ross MI, McNeese MD, Buzdar AU, Hortobagyi GN, Singletary SE (1999) Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460–469PubMed

Miyoshi Y, Ando A, Takamura Y, Taguchi T, Tamaki Y, Noguchi S (2002) Prediction of response to docetaxel by CYP3A4 mRNA expression in breast cancer tissues. Int J Cancer 97:129–132PubMedCrossRef

Molino A, Micciolo R, Turazza M, Bonetti F, Piubello Q, Bonetti A, Nortilli R, Pelosi G, Cetto GL (1997) Ki-67 immunostaining in 322 primary breast cancers: associations with clinical and pathological variables and prognosis. Int J Cancer 74:433–437PubMedCrossRef

Murata K, Sato T, Kanamaru R (1994) Effect of a new anticancer drug, docetaxel (RP56976), on human leukemia cell lines. Gan To Kagaku Ryoho 21:307–313PubMed

Penault-Llorca F, Cayre A, Bouchet Mishellany F, Amat S, Feillel V, Le Bouedec G, Ferriere JP, De Latour M, Chollet P (2003) Induction chemotherapy for breast carcinoma: predictive markers and relation with outcome. Int J Oncol 22:1319–1325PubMed

Prisack HB, Karreman C, Modlich O, Audretsch W, Danae M, Rezai M, Bojar H (2005) Predictive biological markers for response of invasive breast cancer to anthracycline/ cyclophosphamide-based primary (radio-)chemotherapy. Anticancer Res 25:4615–4621PubMed

Ravdin PM, Valero V (1995) Review of docetaxel (Taxotere), a highly active new agent for the treatment of metastatic breast cancer. Semin Oncol Suppl 4:17–21

Ravdin PM, Burris HA 3IIIrd, Cook G, Eisenberg P, Kane M, Bierman WA, Mortimer J, Genevois E, Bellet RE (1995) Phase II trial of docetaxel in advanced anthracycline-resistant or anthracenedione-resistant breast cancer. J Clin Oncol 13: 2879–2885PubMed

Seidman AD, Hudis C, Crown JPA (1993) Phase II evaluation of Taxotere (RP56976 NSC 628503) as initial chemotherapy for metastatic breast cancer. Proc Am Soc Clin Oncol 12:63

Takamura Y, Kobayashi H, Taguchi T, Motomura K, Inaji H, Noguchi S (2002) Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in human breast cancers. Int J Cancer 98:450–455PubMedCrossRef

Tatsuka M, Sato S, Kitajima S, Suto S, Kawai H, Miyauchi M, Ogawa I, Maeda M, Ota T, Takata T (2005) Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is implicated in oral carcinogenesis. Oncogene 24:1122–1127PubMedCrossRef

ten Bokkel Huinink WW, Prove AM, Piccart M, Steward W, Tursz T, Wanders J, Franklin H, Clavel M, Verweij J, Alakl M, Bayssas M, Kaye SB (1994) A phase II trial with docetaxel (Taxotere) in second line treatment with chemotherapy for advanced breast cancer. A study of the ORTC Early Clinical Trials Group. Ann Oncol 5:527–532PubMed

Tong T, Zhong Y, Kong J, Dong L, Song Y, Fu M, Liu Z, Wang M, Guo L, Lu S, Wu M, Zhan Q (2004) Overexpression of Aurora-A contributes to malignant development of human esophageal squamous cell carcinoma. Clin Cancer Res 10:7304–7310 Erratum in (2005) Clin Cancer Res 11:4635PubMedCrossRef

Tsuda H, Sasano H, Akiyama F, Kurosumi M, Hasegawa T, Osamura RY, Sakamoto G (2002) Evaluation of interobserver agreement in scoring immunohistochemical results of HER-2/neu (c-erbB-2) expression detected by HercepTest, Nichirei polyclonal antibody, CB11 and TAB250 in breast carcinoma. Pathol Int 52:126–134PubMedCrossRef

van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L (2001) Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 19:4224–4237PubMed

Vincent-Salomon A, Rousseau A, Jouve M, Beuzeboc P, Sigal-Zafrani B, Freneaux P, Rosty C, Nos C, Campana F, Klijanienko J, Al Ghuzlan A, Sastre-Garau X, Breast Cancer Study Group (2004) Proliferation markers predictive of the pathological response and disease outcome of patients with breast carcinomas treated by anthracycline-based preoperative chemotherapy. Eur J Cancer 40:1502–1508PubMedCrossRef

Title: Low nuclear grade but not cell proliferation predictive of pathological complete response to docetaxel in human breast cancers
Authors: Yasuo Miyoshi
Masafumi Kurosumi
Junichi Kurebayashi
Nariaki Matsuura
Masato Takahashi
Eriko Tokunaga
Chiyomi Egawa
Norikazu Masuda
Seung Jin Kim
Masatsugu Okishiro
Tetsu Yanagisawa
Satsuki Ueda
Tetsuya Taguchi
Yasuhiro Tamaki
Shinzaburo Noguchi
The Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society
Publication date: 01-05-2008
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 5/2008
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-007-0319-5

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