J Breast Cancer.  2016 Dec;19(4):394-401. 10.4048/jbc.2016.19.4.394.

Prognostic Significance of Inner Quadrant Involvement in Breast Cancer Treated with Neoadjuvant Chemotherapy

• Chang JH
• Jeon W
• Kim K
• Shin KH
• Han W
• Noh DY
• Im SA
• Kim TY
• Bang YJ

• KMID: 2362925
• DOI: http://doi.org/10.4048/jbc.2016.19.4.394

Abstract

PURPOSE
In the present study, we aimed to evaluate the initial tumor location as a prognostic factor in breast cancer patients treated with neoadjuvant chemotherapy (NAC).
METHODS
Between March 2002 and January 2007, a total of 179 patients with stage II/III breast cancer underwent NAC followed by breast surgery. Using physical and radiologic findings, patients were grouped by their initial tumor location into inner/both quadrant (upper/lower inner quadrant involvement +/− multicentric tumor involving outer quadrant; n=97) and outer quadrant (n=82) tumor groups. All patients received neoadjuvant docetaxel/doxorubicin chemotherapy. One hundred two patients underwent modified radical mastectomy and 77 patients underwent breast-conserving surgery. Adjuvant radiotherapy (RT) and hormonal therapy were administered after surgery when indicated. While 156 patients underwent postoperative RT, 23 did not. The median follow-up duration was 61.1 (12-106) months.
RESULTS
The 5-year disease-free survival (DFS) and overall survival rates of all patients were 74.8% and 89.9%, respectively. Patients with inner/both quadrant tumors had lower 5-year DFS than those with outer quadrant tumors (67.7% vs. 83.4%, respectively; hazard ratio [HR]=1.941, p=0.034). A nodal ratio >25% was also an independent adverse prognostic factor for DFS (HR=3.276; p<0.001). There was no significant difference in DFS (p=0.592) after RT on the internal mammary node (IMN). Treatment failed in 44 out of 179 patients (24.6%), of which 27 patients had inner/both quadrant tumors. Twenty-one out of 27 patients had distant failures.
CONCLUSION
Among breast cancer patients treated with NAC, those with inner/both quadrant tumors had lower DFS than those with outer quadrant tumors. More aggressive neoadjuvant and/or adjuvant chemotherapy with IMN RT is required for improved disease control and long-term survival.

Keyword

Breast neoplasms; Neoadjuvant therapy; Prognosis; Tumor location

MeSH Terms

Breast Neoplasms*
Breast*
Chemotherapy, Adjuvant
Disease-Free Survival
Drug Therapy*
Follow-Up Studies
Humans
Mastectomy, Modified Radical
Mastectomy, Segmental
Neoadjuvant Therapy
Prognosis
Radiotherapy, Adjuvant
Survival Rate

Figure

• 

  Figure 1 Survival curves according to tumor location. (A) Disease-free survival. (B) Distant metastases-free survival. (C) Locoregional recurrence-free survival. (D) Overall survival.

Reference

1. Gralow JR, Burstein HJ, Wood W, Hortobagyi GN, Gianni L, von Minckwitz G, et al. Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol. 2008; 26:814–819. PMID: 18258991.

2. Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005; 97:188–194. PMID: 15687361.

3. Chia S, Swain SM, Byrd DR, Mankoff DA. Locally advanced and inflammatory breast cancer. J Clin Oncol. 2008; 26:786–790. PMID: 18258987.

4. Buchholz TA, Lehman CD, Harris JR, Pockaj BA, Khouri N, Hylton NF, et al. Statement of the science concerning locoregional treatments after preoperative chemotherapy for breast cancer: a National Cancer Institute conference. J Clin Oncol. 2008; 26:791–797. PMID: 18258988.

5. Gaffney DK, Tsodikov A, Wiggins CL. Diminished survival in patients with inner versus outer quadrant breast cancers. J Clin Oncol. 2003; 21:467–472. PMID: 12560437.

6. Lohrisch C, Jackson J, Jones A, Mates D, Olivotto IA. Relationship between tumor location and relapse in 6,781 women with early invasive breast cancer. J Clin Oncol. 2000; 18:2828–2835. PMID: 10920130.

7. Bräutigam E, Track C, Seewald DH, Feichtinger J, Spiegl K, Hammer J. Medial tumor localization in breast cancer: an unappreciated risk factor? Strahlenther Onkol. 2009; 185:663–668. PMID: 19806331.

8. Zucali R, Mariani L, Marubini E, Kenda R, Lozza L, Rilke F, et al. Early breast cancer: evaluation of the prognostic role of the site of the primary tumor. J Clin Oncol. 1998; 16:1363–1366. PMID: 9552038.

9. Keam B, Im SA, Kim HJ, Oh DY, Kim JH, Lee SH, et al. Clinical significance of axillary nodal ratio in stage II/III breast cancer treated with neoadjuvant chemotherapy. Breast Cancer Res Treat. 2009; 116:153–160. PMID: 18787948.

10. Farrús B, Vidal-Sicart S, Velasco M, Zanón G, Fernández PL, Muñoz M, et al. Incidence of internal mammary node metastases after a sentinel lymph node technique in breast cancer and its implication in the radiotherapy plan. Int J Radiat Oncol Biol Phys. 2004; 60:715–721. PMID: 15465187.

11. Heuts EM, van der Ent FW, von Meyenfeldt MF, Voogd AC. Internal mammary lymph drainage and sentinel node biopsy in breast cancer: a study on 1008 patients. Eur J Surg Oncol. 2009; 35:252–257. PMID: 18684584.

12. Turner-Warwick RT. The lymphatics of the breast. Br J Surg. 1959; 46:574–582. PMID: 13839973.

13. Huang O, Wang L, Shen K, Lin H, Hu Z, Liu G, et al. Breast cancer subpopulation with high risk of internal mammary lymph nodes metastasis: analysis of 2,269 Chinese breast cancer patients treated with extended radical mastectomy. Breast Cancer Res Treat. 2008; 107:379–387. PMID: 17457670.

14. Poortmans PM, Collette S, Kirkove C, Van Limbergen E, Budach V, Struikmans H, et al. Internal mammary and medial Ssupraclavicular irradiation in breast cancer. N Engl J Med. 2015; 373:317–327. PMID: 26200978.

15. Keam B, Im SA, Kim HJ, Oh DY, Kim JH, Lee SH, et al. Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer. BMC Cancer. 2007; 7:203. PMID: 17976237.

16. Chung Y, Kim JW, Shin KH, Kim SS, Ahn SJ, Park W, et al. Dummy run of quality assurance program in a phase 3 randomized trial investigating the role of internal mammary lymph node irradiation in breast cancer patients: Korean Radiation Oncology Group 08-06 study. Int J Radiat Oncol Biol Phys. 2015; 91:419–426. PMID: 25636764.

17. Kim WH, Han W, Chang JM, Cho N, Park IA, Moon WK. Location of triple-negative breast cancers: comparison with estrogen receptor-positive breast cancers on MR imaging. PLoS One. 2015; 10:e0116344. PMID: 25608004.

18. Lim ST, Choi JE, Kim SJ, Kim HA, Kim JY, Park HK, et al. Prognostic implication of the tumor location according to molecular subtypes in axillary lymph node-positive invasive ductal cancer in a Korean population. Breast Cancer Res Treat. 2016; 156:473–483. PMID: 27041335.

19. Tsai J, Bertoni D, Hernandez-Boussard T, Telli ML, Wapnir IL. Lymph node ratio analysis after neoadjuvant chemotherapy is prognostic in hormone receptor-positive and triple-negative breast cancer. Ann Surg Oncol. 2016; 23:3310–3316. PMID: 27401442.

20. Kim SH, Jung KH, Kim TY, Im SA, Choi IS, Chae YS, et al. Prognostic value of axillary nodal ratio after neoadjuvant chemotherapy of doxorubicin/cyclophosphamide followed by docetaxel in breast cancer: a multicenter retrospective cohort study. Cancer Res Treat. 2016; 48:1373–1381. PMID: 27034147.

21. Haffty BG, McCall LM, Ballman KV, McLaughlin S, Jagsi R, Ollila DW, et al. Patterns of local-regional management following neoadjuvant chemotherapy in breast cancer: results from ACOSOG Z1071 (Alliance). Int J Radiat Oncol Biol Phys. 2016; 94:493–502. PMID: 26867878.

22. Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, et al. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol. 2002; 20:1456–1466. PMID: 11896092.

23. Reitsamer R, Peintinger F, Prokop E, Hitzl W. Pathological complete response rates comparing 3 versus 6 cycles of epidoxorubicin and docetaxel in the neoadjuvant setting of patients with stage II and III breast cancer. Anticancer Drugs. 2005; 16:867–870. PMID: 16096435.

24. Gonzalez-Angulo AM, McGuire SE, Buchholz TA, Tucker SL, Kuerer HM, Rouzier R, et al. Factors predictive of distant metastases in patients with breast cancer who have a pathologic complete response after neoadjuvant chemotherapy. J Clin Oncol. 2005; 23:7098–7104. PMID: 16192593.