Predictors of Locoregional Recurrence After Failure to Achieve Pathologic Complete Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

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  • a Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, Missouri;
  • b Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina; and
  • c Department of Surgery, and
  • d Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri.
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Background: This study evaluated factors predictive of locoregional recurrence (LRR) in women with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy who do not experience pathologic complete response (pCR). Methods: This is a single-institution retrospective review of women with TNBC treated with neoadjuvant chemotherapy, surgery, and radiation therapy in 2000 through 2013. LRR was estimated between patients with and without pCR using the Kaplan-Meier method. Patient-, tumor-, and treatment-specific factors in patients without pCR were analyzed using the Cox proportional hazards method to evaluate factors predictive of LRR. Log-rank statistics were then used to compare LRR among these risk factors. Results: A total of 153 patients with a median follow-up of 48.6 months were included. The 4-year overall survival and LRR were 70% and 15%, respectively, and the 4-year LRR in patients with pCR was 0% versus 22.0% in those without (P<.001). In patients without pCR, lymphovascular space invasion (LVSI; hazard ratio, 3.92; 95% CI, 1.64–9.38; P=.002) and extranodal extension (ENE; hazard ratio, 3.32; 95% CI, 1.35–8.15; P=.009) were significant predictors of LRR in multivariable analysis. In these patients, the 4-year LRR with LVSI was 39.8% versus 15.0% without (P<.001). Similarly, the 4-year LRR was 48.1% with ENE versus 16.1% without (P=.002). In patients without pCR, the presence of both LVSI and ENE were associated with an even further increased risk of LRR compared with patients with either LVSI or ENE alone and those with neither LVSI nor ENE in the residual tumor (P<.001). Conclusions: In patients without pCR, the presence of LVSI and ENE increases the risk of LRR in TNBC. The risk of LRR is compounded when both LVSI and ENE are present in the same patient. Future clinical trials are warranted to lower the risk of LRR in these high-risk patients.

Correspondence: Imran Zoberi, MD, Department of Radiation Oncology, Washington University School of Medicine, 4921 Parkview Place, Saint Louis, MO 63110. Email: izoberi@wustl.edu

These authors contributed equally.

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    • Supplemental Table (PDF 926 KB)
  • 1.

    Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med 2010;363:19381948.

  • 2.

    Liedtke C, Mazouni C, Hess KR, . Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 2008;26:12751281.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    McGuire A, Lowery AJ, Kell MR, . Locoregional recurrence following breast cancer surgery in the trastuzumab era: a systematic review by subtype. Ann Surg Oncol 2017;24:31243132.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Caudle AS, Yu TK, Tucker SL, . Local-regional control according to surrogate markers of breast cancer subtypes and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast conserving therapy. Breast Cancer Res 2012;14:R83.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Kyndi M, Sørensen FB, Knudsen H, . Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. J Clin Oncol 2008;26:14191426.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Chaudhary LN, Wilkinson KH, Kong A. Triple-negative breast cancer: who should receive neoadjuvant chemotherapy? Surg Oncol Clin N Am 2018;27:141153.

  • 7.

    von Minckwitz G, Untch M, Blohmer JU, . Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 2012;30:17961804.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Mamounas EP, Anderson SJ, Dignam JJ, . Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol 2012;30:39603966.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Xiangying M, Shikai W, Zefei J, . Progestin as an alternative treatment option for multi-treated recurrent triple-negative breast cancer. Swiss Med Wkly 2013;143:w13765.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Braunstein LZ, Niemierko A, Shenouda MN, . Outcome following local-regional recurrence in women with early-stage breast cancer: impact of biologic subtype. Breast J 2015;21:161167.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Aft R, Naughton M, Trinkaus K, . Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial. Lancet Oncol 2010;11:421428.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Chen VE, Gillespie EF, Zakeri K, . Pathologic response after neoadjuvant chemotherapy predicts locoregional control in patients with triple negative breast cancer. Adv Radiat Oncol 2017;2:105109.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Abdulkarim BS, Cuartero J, Hanson J, . Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. J Clin Oncol 2011;29:28522858.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Chen X, Yu X, Chen J, . Analysis in early stage triple-negative breast cancer treated with mastectomy without adjuvant radiotherapy: patterns of failure and prognostic factors. Cancer 2013;119:23662374.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Hamy AS, Lam GT, Laas E, . Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated with poor prognosis in breast carcinoma. Breast Cancer Res Treat 2018;169:295304.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Aleskandarany MA, Sonbul SN, Mukherjee A, . Molecular mechanisms underlying lymphovascular invasion in invasive breast cancer. Pathobiology 2015;82:113123.

  • 17.

    Choi AH, Surrusco M, Rodriguez S, . Extranodal extension on sentinel lymph node dissection: why should we treat it differently? Am Surg 2014;80:932935.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Nottegar A, Veronese N, Senthil M, . Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: a systematic review and an exploratory meta-analysis. Eur J Surg Oncol 2016;42:919925.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Al-Hilli Z, Hieken TJ, Hoskin TL, . Impact of neoadjuvant chemotherapy on pathologic axillary nodal status in HER-2 positive patients presenting with clinically node-negative disease. J Surg Oncol 2015;112:453457.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Ibrahim E, Al-Gahmi AM, Zeenelin AA, . Basal vs. luminal A breast cancer subtypes: a matched case-control study using estrogen receptor, progesterone receptor, and HER-2 as surrogate markers. Med Oncol 2009;26:372378.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Sikov WM, Berry DA, Perou CM, . Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol 2015;33:1321.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    von Minckwitz G, Schneeweiss A, Loibl S, . Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol 2014;15:747756.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Poggio F, Bruzzone M, Ceppi M, . Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis. Ann Oncol 2018;29:14971508.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Loibl S, O’Shaughnessy J, Untch M, . Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol 2018;19:497509.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Masuda N, Lee SJ, Ohtani S, . Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 2017;376:21472159.

  • 26.

    Gradishar WJ, Anderson BO, Abraham J, . NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 4.2018. Accessed April 15, 2018. To view the most recent version of these guidelines, visit NCCN.org.

  • 27.

    Yan M, Abdi MA, Falkson C. Axillary management in breast cancer patients: a comprehensive review of the key trials. Clin Breast Cancer 2018;18:e12511259.

  • 28.

    Boughey JC, Suman VJ, Mittendorf EA, . Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA 2013;310:14551461.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Brackstone M, Palma D, Tuck AB, . Concurrent neoadjuvant chemotherapy and radiation therapy in locally advanced breast cancer. Int J Radiat Oncol Biol Phys 2017;99:769776.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Woodward WA, Fang P, Arriaga L, . A phase 2 study of preoperative capecitabine and concomitant radiation in women with advanced breast cancer. Int J Radiat Oncol Biol Phys 2017;99:777783.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Gaui MF, Amorim G, Arcuri RA, . A phase II study of second-line neoadjuvant chemotherapy with capecitabine and radiation therapy for anthracycline-resistant locally advanced breast cancer. Am J Clin Oncol 2007;30:7881.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Vernon CC, Hand JW, Field SB, . Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. Int J Radiat Oncol Biol Phys 1996;35:731744.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Jones EL, Oleson JR, Prosnitz LR, . Randomized trial of hyperthermia and radiation for superficial tumors. J Clin Oncol 2005;23:30793085.

  • 34.

    Varma S, Myerson R, Moros E, . Simultaneous radiotherapy and superficial hyperthermia for high-risk breast carcinoma: a randomised comparison of treatment sequelae in heated versus non-heated sectors of the chest wall hyperthermia. Int J Hyperthermia 2012;28:583590.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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