Top

Published in:

01-07-2019 | Mastectomy | Clinical Trial

Local–regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial)

Authors: Jennifer R. Bellon, Hao Guo, William T. Barry, Chau T. Dang, Denise A. Yardley, Beverly Moy, P. Kelly Marcom, Kathy S. Albain, Hope S. Rugo, Matthew Ellis, Antonio C. Wolff, Lisa A. Carey, Beth A. Overmoyer, Ann H. Partridge, Clifford A. Hudis, Ian Krop, Harold J. Burstein, Eric P. Winer, Sara M. Tolaney

Published in: Breast Cancer Research and Treatment | Issue 2/2019

Abstract

Purpose

Women with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local–regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T).

Methods

Patients with HER2-positive tumors ≤ 3.0 cm with negative axillary nodes or micrometastatic disease were eligible. Systemic therapy included weekly T and H for 12 weeks followed by continuation of H to complete 1 year. Radiation therapy (RT) was required following breast-conserving surgery (BCS), but dose and fields were not specified. Disease-free survival (DFS) and LRR-free survival were calculated using the Kaplan–Meier method.

Results

Of the 410 patients enrolled from September 2007 to September 2010, 406 initiated protocol therapy and formed the basis of this analysis. A total of 272 (67%) had hormone receptor-positive tumors. Of 162 patients undergoing mastectomy, local therapy records were unavailable for two. None of the 160 for whom records were available received RT. Among 244 BCS patients, detailed RT records were available for 217 (89%). With a median follow-up of 6.5 years, 7-year DFS was 93.3% (95% CI 90.4–96.2), and LRR-free survival was 98.6% (95% CI 97.4–99.8).

Conclusion

LRR in this select group of early-stage patients with HER2-positive disease receiving effective anti-HER2 therapy is extremely low. If confirmed in additional studies, future investigational efforts should focus on de-escalating local therapy.

Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale AL, Botstein D (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100(14):8418–8423. https://doi.org/10.1073/pnas.0932692100 CrossRefPubMedPubMedCentral

Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, Bellon JR, Wong JS, Smith BL, Harris JR (2008) Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol 26(14):2373–2378. https://doi.org/10.1200/JCO.2007.14.4287 CrossRefPubMed

Millar EK, Graham PH, O’Toole SA, McNeil CM, Browne L, Morey AL, Eggleton S, Beretov J, Theocharous C, Capp A, Nasser E, Kearsley JH, Delaney G, Papadatos G, Fox C, Sutherland RL (2009) Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage invasive breast cancer using a five-biomarker panel. J Clin Oncol 27(28):4701–4708. https://doi.org/10.1200/JCO.2008.21.7075 CrossRefPubMed

Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H (2010) Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 28(10):1684–1691. https://doi.org/10.1200/JCO.2009.24.9284 CrossRefPubMed

Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365(9472):1687–1717. https://doi.org/10.1016/S0140-6736(05)66544-0 CrossRef

Sartor CI, Peterson BL, Woolf S, Fitzgerald TJ, Laurie F, Turrisi AJ, Bogart J, Henderson IC, Norton L (2005) Effect of addition of adjuvant paclitaxel on radiotherapy delivery and locoregional control of node-positive breast cancer: cancer and leukemia group B 9344. J Clin Oncol 23(1):30–40. https://doi.org/10.1200/JCO.2005.12.044 CrossRefPubMed

Anderson SJ, Wapnir I, Dignam JJ, Fisher B, Mamounas EP, Jeong JH, Geyer CE Jr, Wickerham DL, Costantino JP, Wolmark N (2009) Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer. J Clin Oncol 27(15):2466–2473. https://doi.org/10.1200/JCO.2008.19.8424 CrossRefPubMedPubMedCentral

Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684. https://doi.org/10.1056/NEJMoa052122 CrossRefPubMed

Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Guo H, Hudis CA, Krop IE, Burstein HJ, Winer EP (2015) Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med 372(2):134–141. https://doi.org/10.1056/NEJMoa1406281 CrossRefPubMedPubMedCentral

10.

Tseng YD, Uno H, Hughes ME, Niland JC, Wong YN, Theriault R, Blitzblau RC, Moy B, Breslin T, Edge SB, Hassett MJ, Punglia RS (2015) Biological subtype predicts risk of locoregional recurrence after mastectomy and impact of postmastectomy radiation in a large national database. Int J Radiat Oncol Biol Phys 93(3):622–630. https://doi.org/10.1016/j.ijrobp.2015.07.006 CrossRefPubMed

11.

Yin W, Jiang Y, Shen Z, Shao Z, Lu J (2011) Trastuzumab in the adjuvant treatment of HER2-positive early breast cancer patients: a meta-analysis of published randomized controlled trials. PLoS ONE 6(6):e21030. https://doi.org/10.1371/journal.pone.0021030 CrossRefPubMedPubMedCentral

12.

Fyles AW, McCready DR, Manchul LA, Trudeau ME, Merante P, Pintilie M, Weir LM, Olivotto IA (2004) Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med 351(10):963–970. https://doi.org/10.1056/NEJMoa040595 CrossRefPubMed

13.

Liu FF, Shi W, Done SJ, Miller N, Pintilie M, Voduc D, Nielsen TO, Nofech-Mozes S, Chang MC, Whelan TJ, Weir LM, Olivotto IA, McCready DR, Fyles AW (2015) Identification of a low-risk luminal a breast cancer cohort that may not benefit from breast radiotherapy. J Clin Oncol 33(18):2035–2040. https://doi.org/10.1200/JCO.2014.57.7999 CrossRefPubMed

14.

Whelan TJ, Olivotto IA, Parulekar WR, Ackerman I, Chua BH, Nabid A, Vallis KA, White JR, Rousseau P, Fortin A, Pierce LJ, Manchul L, Chafe S, Nolan MC, Craighead P, Bowen J, McCready DR, Pritchard KI, Gelmon K, Murray Y, Chapman JA, Chen BE, Levine MN, Investigators MAS (2015) Regional nodal irradiation in early-stage breast cancer. N Engl J Med 373(4):307–316. https://doi.org/10.1056/NEJMoa1415340 CrossRefPubMedPubMedCentral

15.

Poortmans PM, Collette S, Kirkove C, Van Limbergen E, Budach V, Struikmans H, Collette L, Fourquet A, Maingon P, Valli M, De Winter K, Marnitz S, Barillot I, Scandolaro L, Vonk E, Rodenhuis C, Marsiglia H, Weidner N, van Tienhoven G, Glanzmann C, Kuten A, Arriagada R, Bartelink H, Van den Bogaert W, Oncology ER, Breast Cancer G (2015) Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med 373(4):317–327. https://doi.org/10.1056/NEJMoa1415369 CrossRefPubMed

16.

Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N (2002) Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med 347(8):567–575. https://doi.org/10.1056/NEJMoa020128 CrossRefPubMed

17.

Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366(9503):2087–2106. https://doi.org/10.1016/S0140-6736(05)67887-7 CrossRefPubMed

18.

Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, Kamby C, Kjaer M, Gadeberg CC, Rasmussen BB, Blichert-Toft M, Mouridsen HT (1999) Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 353(9165):1641–1648. https://doi.org/10.1016/S0140-6736(98)09201-0 CrossRefPubMed

19.

Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB, Zedeler K (1997) Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 337(14):949–955. https://doi.org/10.1056/NEJM199710023371401 CrossRefPubMed

20.

Punglia RS, Morrow M, Winer EP, Harris JR (2007) Local therapy and survival in breast cancer. N Engl J Med 356(23):2399–2405. https://doi.org/10.1056/NEJMra065241 CrossRefPubMed

Title: Local–regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial)
Authors: Jennifer R. Bellon
Hao Guo
William T. Barry
Chau T. Dang
Denise A. Yardley
Beverly Moy
P. Kelly Marcom
Kathy S. Albain
Hope S. Rugo
Matthew Ellis
Antonio C. Wolff
Lisa A. Carey
Beth A. Overmoyer
Ann H. Partridge
Clifford A. Hudis
Ian Krop
Harold J. Burstein
Eric P. Winer
Sara M. Tolaney
Publication date: 01-07-2019
Publisher: Springer US
Keywords: Mastectomy
Systemic Therapy
Breast Cancer
Breast Cancer
Trastuzumab
Published in: Breast Cancer Research and Treatment / Issue 2/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05238-4

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2019

Real-world clinical outcomes and toxicity in metastatic breast cancer patients treated with palbociclib and endocrine therapy

Post-mastectomy immediate breast reconstruction is oncologically safe in well-selected T4 locally advanced breast cancer: a large population-based study and matched case–control analysis

Shared-patient physician networks and their impact on the uptake of genomic testing in breast cancer

Racial disparities in surveillance mammography among older breast cancer survivors

Circulating adipose stromal cells as a response biomarker in phase II energy balance trials of obese breast cancer survivors and high-risk women

A novel RNA aptamer identifies plasma membrane ATP synthase beta subunit as an early marker and therapeutic target in aggressive cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer