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.
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.
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.
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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
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.
Egan RL. Multicentric breast carcinomas: clinical-radiographic-pathologic whole-organ studies and 10-year survival. Cancer. 1982;49:1123–30.
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.
McDivitt RW. Breast cancer multicentricity. Monogr Pathol. 1984(25):139–148.
Sarnelli R, Squartini F. Multicentricity in breast cancer: a submacroscopic study. Pathol Ann. 1986;21(Pt 1):143–58.
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.
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.
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.
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.
Kurtz JM, Jacquemier J, Amalric R, et al. Breast-conserving therapy for macroscopically multiple cancers. Ann Surg. 1990;212:38–44.
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.
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.
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.
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.
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.
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.
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.
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.
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.
von Minckwitz G, Blohmer JU, Costa SD, et al. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol. 2013;31:3623–30.
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.
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.
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.
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.
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.
Kadioglu H, Yucel S, Yildiz S, et al. Feasibility of breast conserving surgery in multifocal breast cancers. Am J Surg. 2014;208:457–64.
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, Hsu L, et al. Breast cancer multifocality and multicentricity and locoregional recurrence. Oncologist. 2013;18:1167–73.
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.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Ataseven, B., Lederer, B., Blohmer, J.U. et al. Impact of Multifocal or Multicentric Disease on Surgery and Locoregional, Distant and Overall Survival of 6,134 Breast Cancer Patients Treated With Neoadjuvant Chemotherapy. Ann Surg Oncol 22, 1118–1127 (2015). https://doi.org/10.1245/s10434-014-4122-7
- Pathologic Complete Response
- Breast Conservation
- Multifocal Disease
- Multifocal Tumor
- Multicentric Disease