Skip to main content
Top
Published in: Annals of Surgical Oncology 4/2015

01-04-2015 | Breast Oncology

Impact of Multifocal or Multicentric Disease on Surgery and Locoregional, Distant and Overall Survival of 6,134 Breast Cancer Patients Treated With Neoadjuvant Chemotherapy

Authors: Beyhan Ataseven, MD, Bianca Lederer, MD, Jens U. Blohmer, MD, PhD, Carsten Denkert, MD, PhD, Bernd Gerber, MD, PhD, Jörg Heil, MD, Thorsten Kühn, MD, PhD, Sherko Kümmel, MD, Mahdi Rezai, MD, Sibylle Loibl, MD, PhD, Gunter von Minckwitz, MD, PhD

Published in: Annals of Surgical Oncology | Issue 4/2015

Login to get access

Abstract

Background

The impact of tumor focality on type of surgery, local recurrence rate, and survival after neoadjuvant chemotherapy (NACT) for breast cancer is not fully understood. This study aimed to compare local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) according to focality stratified by type of surgery and pathologic complete response (pCR), with a focus on breast conservation.

Methods

Participants (n = 6,134) in the GeparTrio, GeparQuattro, and GeparQuinto trials with operable or locally advanced tumors receiving NACT were classified as having unifocal (1 lesion), multifocal (≥2 lesions in 1 quadrant), or multicentric (≥1 lesion in ≥2 quadrants) disease. The study investigated LRFS, DFS, and OS according to focality stratified by type of surgery and pathologic complete response.

Results

The patients were classified as having unifocal (n = 4,733, 77.1 %), multifocal (n = 820, 13.4 %), or multicentric (n = 581, 9.5 %) tumors. The respective pCR rates were 19.4, 16.5, and 14.4 %. Breast conservation was performed for 71.6, 58.5, and 30 % of these patients, respectively (P < 0.001). The LRFS rate was 92.9 % for the unifocal, 95.1 % for the multifocal, and 90.4 % for the multicentric tumors (P = 0.002). The patients with multicentric tumors but not the patients with multifocal tumors had worse DFS (P < 0.001) and OS (P = 0.009) than the patients with unifocal tumors. However, LRFS, DFS, and OS were not inferior for the patients with multicentric or multifocal tumors if pCR was achieved or breast conservation was performed after NACT.

Conclusion

Breast conservation is feasible for clinically multifocal or multicentric breast cancer patients who undergo NACT without worsening LRFS if tumor-free margins can be attained or if patients achieve a pCR.
Appendix
Available only for authorised users
Literature
1.
go back to reference Anastassiades O, Iakovou E, Stavridou N, Gogas J, Karameris A. Multicentricity in breast cancer. A study of 366 cases. Am J Clin Pathol. 1993;99:238–43.PubMed Anastassiades O, Iakovou E, Stavridou N, Gogas J, Karameris A. Multicentricity in breast cancer. A study of 366 cases. Am J Clin Pathol. 1993;99:238–43.PubMed
2.
go back to reference Egan RL. Multicentric breast carcinomas: clinical-radiographic-pathologic whole-organ studies and 10-year survival. Cancer. 1982;49:1123–30.CrossRefPubMed Egan RL. Multicentric breast carcinomas: clinical-radiographic-pathologic whole-organ studies and 10-year survival. Cancer. 1982;49:1123–30.CrossRefPubMed
3.
go back to reference Fisher ER, Gregorio R, Redmond C, Vellios F, Sommers SC, Fisher B. Pathologic findings from the National Surgical Adjuvant Breast Project (protocol no. 4): I. Observations concerning the multicentricity of mammary cancer. Cancer. 1975;35:247–54.CrossRefPubMed Fisher ER, Gregorio R, Redmond C, Vellios F, Sommers SC, Fisher B. Pathologic findings from the National Surgical Adjuvant Breast Project (protocol no. 4): I. Observations concerning the multicentricity of mammary cancer. Cancer. 1975;35:247–54.CrossRefPubMed
4.
go back to reference McDivitt RW. Breast cancer multicentricity. Monogr Pathol. 1984(25):139–148.PubMed McDivitt RW. Breast cancer multicentricity. Monogr Pathol. 1984(25):139–148.PubMed
5.
go back to reference Sarnelli R, Squartini F. Multicentricity in breast cancer: a submacroscopic study. Pathol Ann. 1986;21(Pt 1):143–58. Sarnelli R, Squartini F. Multicentricity in breast cancer: a submacroscopic study. Pathol Ann. 1986;21(Pt 1):143–58.
6.
go back to reference Spinelli C, Berti P, Ricci E, Miccoli P. Multicentric breast tumour: an anatomical-clinical study of 100 cases. Eur J Surg Oncol. 1992;18:23–6.PubMed Spinelli C, Berti P, Ricci E, Miccoli P. Multicentric breast tumour: an anatomical-clinical study of 100 cases. Eur J Surg Oncol. 1992;18:23–6.PubMed
7.
go back to reference Vaidya JS, Vyas JJ, Chinoy RF, Merchant N, Sharma OP, Mittra I. Multicentricity of breast cancer: whole-organ analysis and clinical implications. Br J Cancer. 1996;74:820–4.CrossRefPubMedCentralPubMed Vaidya JS, Vyas JJ, Chinoy RF, Merchant N, Sharma OP, Mittra I. Multicentricity of breast cancer: whole-organ analysis and clinical implications. Br J Cancer. 1996;74:820–4.CrossRefPubMedCentralPubMed
8.
go back to reference Wilson LD, Beinfield M, McKhann CF, Haffty BG. Conservative surgery and radiation in the treatment of synchronous ipsilateral breast cancers. Cancer. 1993;72:137–42.CrossRefPubMed Wilson LD, Beinfield M, McKhann CF, Haffty BG. Conservative surgery and radiation in the treatment of synchronous ipsilateral breast cancers. Cancer. 1993;72:137–42.CrossRefPubMed
9.
go back to reference Leopold KA, Recht A, Schnitt SJ, et al. Results of conservative surgery and radiation therapy for multiple synchronous cancers of one breast. Int J Radiat Oncol Biol Phys. 1989;16:11–6.CrossRefPubMed Leopold KA, Recht A, Schnitt SJ, et al. Results of conservative surgery and radiation therapy for multiple synchronous cancers of one breast. Int J Radiat Oncol Biol Phys. 1989;16:11–6.CrossRefPubMed
11.
go back to reference Gentilini O, Botteri E, Rotmensz N, et al. Conservative surgery in patients with multifocal/multicentric breast cancer. Breast Cancer Res Treat. 2009;113:577–83.CrossRefPubMed Gentilini O, Botteri E, Rotmensz N, et al. Conservative surgery in patients with multifocal/multicentric breast cancer. Breast Cancer Res Treat. 2009;113:577–83.CrossRefPubMed
12.
go back to reference Yerushalmi R, Tyldesley S, Woods R, Kennecke HF, Speers C, Gelmon KA. Is breast-conserving therapy a safe option for patients with tumor multicentricity and multifocality? Ann Oncol. 2012;23:876–81.CrossRefPubMed Yerushalmi R, Tyldesley S, Woods R, Kennecke HF, Speers C, Gelmon KA. Is breast-conserving therapy a safe option for patients with tumor multicentricity and multifocality? Ann Oncol. 2012;23:876–81.CrossRefPubMed
13.
go back to reference Gianni L, Baselga J, Eiermann W, et al. Feasibility and tolerability of sequential doxorubicin/paclitaxel followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative therapy. Clin Cancer Res. 2005;11(24 Pt 1):8715–21.CrossRefPubMed Gianni L, Baselga J, Eiermann W, et al. Feasibility and tolerability of sequential doxorubicin/paclitaxel followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative therapy. Clin Cancer Res. 2005;11(24 Pt 1):8715–21.CrossRefPubMed
14.
go back to reference Kaufmann M, von Minckwitz G, Mamounas EP, et al. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2012;19:1508–16. Kaufmann M, von Minckwitz G, Mamounas EP, et al. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2012;19:1508–16.
15.
go back to reference Huober J, Fasching PA, Hanusch C, et al. Neoadjuvant chemotherapy with paclitaxel and everolimus in breast cancer patients with nonresponsive tumours to epirubicin/cyclophosphamide (EC) ± bevacizumab – results of the randomised GeparQuinto study (GBG 44). Eur J Cancer. 2013;49:2284–93.CrossRefPubMed Huober J, Fasching PA, Hanusch C, et al. Neoadjuvant chemotherapy with paclitaxel and everolimus in breast cancer patients with nonresponsive tumours to epirubicin/cyclophosphamide (EC) ± bevacizumab – results of the randomised GeparQuinto study (GBG 44). Eur J Cancer. 2013;49:2284–93.CrossRefPubMed
16.
go back to reference Untch M, Loibl S, Bischoff J, et al. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012;13:135–44.CrossRefPubMed Untch M, Loibl S, Bischoff J, et al. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012;13:135–44.CrossRefPubMed
17.
go back to reference Untch M, Rezai M, Loibl S, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010;28:2024–31.CrossRefPubMed Untch M, Rezai M, Loibl S, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010;28:2024–31.CrossRefPubMed
18.
go back to reference von Minckwitz G, Eidtmann H, Rezai M, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012;366:299–309.CrossRef von Minckwitz G, Eidtmann H, Rezai M, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012;366:299–309.CrossRef
19.
go back to reference von Minckwitz G, Rezai M, Loibl S, et al. Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. J Clin Oncol. 2010;28:2015–23.CrossRef von Minckwitz G, Rezai M, Loibl S, et al. Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. J Clin Oncol. 2010;28:2015–23.CrossRef
20.
go back to reference von Minckwitz G, Blohmer JU, Costa SD, et al. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol. 2013;31:3623–30.CrossRef von Minckwitz G, Blohmer JU, Costa SD, et al. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol. 2013;31:3623–30.CrossRef
21.
go back to reference von Minckwitz G, Kummel S, Vogel P, et al. Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Nat Cancer Inst. 2008;100:542–51.CrossRef von Minckwitz G, Kummel S, Vogel P, et al. Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Nat Cancer Inst. 2008;100:542–51.CrossRef
22.
go back to reference von Minckwitz G, Kummel S, Vogel P, et al. Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Nat Cancer Inst. 2008;100:552–62.CrossRef von Minckwitz G, Kummel S, Vogel P, et al. Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Nat Cancer Inst. 2008;100:552–62.CrossRef
23.
go back to reference Oh JL, Dryden MJ, Woodward WA, et al. Locoregional control of clinically diagnosed multifocal or multicentric breast cancer after neoadjuvant chemotherapy and locoregional therapy. J Clin Oncol. 2006;24:4971–5.CrossRefPubMed Oh JL, Dryden MJ, Woodward WA, et al. Locoregional control of clinically diagnosed multifocal or multicentric breast cancer after neoadjuvant chemotherapy and locoregional therapy. J Clin Oncol. 2006;24:4971–5.CrossRefPubMed
24.
go back to reference Weissenbacher T, Zschage M, Janni W, et al. Multicentric and multifocal versus unifocal breast cancer: is the tumor-node-metastasis classification justified? Breast Cancer Res Treat. 2010;122:27–34.CrossRefPubMed Weissenbacher T, Zschage M, Janni W, et al. Multicentric and multifocal versus unifocal breast cancer: is the tumor-node-metastasis classification justified? Breast Cancer Res Treat. 2010;122:27–34.CrossRefPubMed
25.
go back to reference Yerushalmi R, Kennecke H, Woods R, Olivotto I, Speers C, Gelmon K. Does multicentric/multifocal breast cancer differ from unifocal breast cancer? An analysis of survival and contralateral breast cancer incidence. Breast Cancer Res Treat. 2009;117:365–70.CrossRefPubMed Yerushalmi R, Kennecke H, Woods R, Olivotto I, Speers C, Gelmon K. Does multicentric/multifocal breast cancer differ from unifocal breast cancer? An analysis of survival and contralateral breast cancer incidence. Breast Cancer Res Treat. 2009;117:365–70.CrossRefPubMed
26.
go back to reference Kadioglu H, Yucel S, Yildiz S, et al. Feasibility of breast conserving surgery in multifocal breast cancers. Am J Surg. 2014;208:457–64. Kadioglu H, Yucel S, Yildiz S, et al. Feasibility of breast conserving surgery in multifocal breast cancers. Am J Surg. 2014;208:457–64.
27.
go back to reference Lynch SP, Lei X, Chavez-MacGregor M, et al. Multifocality and multicentricity in breast cancer and survival outcomes. Annl Oncol. 2012;23:3063–9. Lynch SP, Lei X, Chavez-MacGregor M, et al. Multifocality and multicentricity in breast cancer and survival outcomes. Annl Oncol. 2012;23:3063–9.
29.
go back to reference Moon HG, Han W, Kim JY, et al. Effect of multiple invasive foci on breast cancer outcomes according to the molecular subtypes: a report from the Korean Breast Cancer Society. Ann of Oncol. 2013;24:2298–304.CrossRef Moon HG, Han W, Kim JY, et al. Effect of multiple invasive foci on breast cancer outcomes according to the molecular subtypes: a report from the Korean Breast Cancer Society. Ann of Oncol. 2013;24:2298–304.CrossRef
Metadata
Title
Impact of Multifocal or Multicentric Disease on Surgery and Locoregional, Distant and Overall Survival of 6,134 Breast Cancer Patients Treated With Neoadjuvant Chemotherapy
Authors
Beyhan Ataseven, MD
Bianca Lederer, MD
Jens U. Blohmer, MD, PhD
Carsten Denkert, MD, PhD
Bernd Gerber, MD, PhD
Jörg Heil, MD
Thorsten Kühn, MD, PhD
Sherko Kümmel, MD
Mahdi Rezai, MD
Sibylle Loibl, MD, PhD
Gunter von Minckwitz, MD, PhD
Publication date
01-04-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 4/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-4122-7

Other articles of this Issue 4/2015

Annals of Surgical Oncology 4/2015 Go to the issue