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

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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%).

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References

  • 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 88:1339–1345

    Article  PubMed  CAS  Google Scholar 

  • 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 21:4165–4174

    Article  PubMed  CAS  Google Scholar 

  • 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 6:2751–2758

    PubMed  Google Scholar 

  • 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 92:147–155

    Article  PubMed  CAS  Google Scholar 

  • 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 362:362–369

    Article  PubMed  CAS  Google Scholar 

  • 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 86:197–206

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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 9:686–692

    PubMed  CAS  Google Scholar 

  • 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 23:171–183

    Article  PubMed  CAS  Google Scholar 

  • 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 16:2672–2685

    PubMed  CAS  Google Scholar 

  • 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 25:1631–1639

    PubMed  CAS  Google Scholar 

  • 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 34:335–343

    Article  PubMed  CAS  Google Scholar 

  • 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 9:2992–2997

    PubMed  CAS  Google Scholar 

  • 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 65:2899–2905

    Article  PubMed  CAS  Google Scholar 

  • 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 15:49–57

    PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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 23:422–431

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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 17:460–469

    PubMed  CAS  Google Scholar 

  • 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 97:129–132

    Article  PubMed  CAS  Google Scholar 

  • 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 74:433–437

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • 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 22:1319–1325

    PubMed  CAS  Google Scholar 

  • 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 25:4615–4621

    PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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: 2879–2885

    PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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 98:450–455

    Article  PubMed  CAS  Google Scholar 

  • 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 24:1122–1127

    Article  PubMed  CAS  Google Scholar 

  • 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 5:527–532

    PubMed  CAS  Google Scholar 

  • 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 11:4635

    Article  PubMed  CAS  Google Scholar 

  • 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 52:126–134

    Article  PubMed  CAS  Google Scholar 

  • 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 19:4224–4237

    PubMed  Google Scholar 

  • 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 40:1502–1508

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported in part by Grants-in-Aid for Scientific Research from the Japanese Breast Cancer Society, for Cancer Research from the Ministry of Health, Labour and Welfare of Japan, and for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Yasuo Miyoshi, Seung Jin Kim, Masatsugu Okishiro, Tetsu Yanagisawa, Satsuki Ueda, Tetsuya Taguchi, Yasuhiro Tamaki & Shinzaburo Noguchi

  2. Department of Pathology, Saitama Cancer Center, Saitama, Japan

    Masafumi Kurosumi

  3. Department of Breast and Thyroid Surgery, Kawasaki Medical School, Matsushima, Kurashiki, Okayama, Japan

    Junichi Kurebayashi

  4. Department of Pathology, School of Allied Health Science, Faculty of Medicine, Osaka University, Osaka, Japan

    Nariaki Matsuura

  5. First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan

    Masato Takahashi

  6. Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan

    Eriko Tokunaga

  7. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

    Chiyomi Egawa

  8. Department of Surgery, Osaka National Hospital, Osaka, Japan

    Norikazu Masuda

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  1. Yasuo Miyoshi
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  9. Seung Jin Kim
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  10. Masatsugu Okishiro
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  11. Tetsu Yanagisawa
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  12. Satsuki Ueda
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  13. Tetsuya Taguchi
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  14. Yasuhiro Tamaki
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  15. Shinzaburo Noguchi
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The Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society

Corresponding author

Correspondence to Shinzaburo Noguchi.

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Miyoshi, Y., Kurosumi, M., Kurebayashi, J. et al. Low nuclear grade but not cell proliferation predictive of pathological complete response to docetaxel in human breast cancers. J Cancer Res Clin Oncol 134, 561–567 (2008). https://doi.org/10.1007/s00432-007-0319-5

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  • DOI: https://doi.org/10.1007/s00432-007-0319-5

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