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Open Access 01-12-2014 | Research

HER-2 positive breast cancer is associated with an increased risk of positive cavity margins after initial lumpectomy

Authors: Haixia Jia, Weijuan Jia, Yaping Yang, Shunrong Li, Huiyi Feng, Jieqiong Liu, Nanyan Rao, Liang Jin, Jiannan Wu, Ru Gu, Liling Zhu, Kai Chen, Heran Deng, Yunjie Zeng, Qiang Liu, Erwei Song, Fengxi Su

Published in: World Journal of Surgical Oncology | Issue 1/2014

Abstract

Background

The effect of breast cancer subtype on margin status after lumpectomy remains unclear. This study aims to determine whether approximated breast cancer subtype is associated with positive margins after lumpectomy, which could be used to determine if there is an increased risk of developing local recurrence (LR) following breast-conserving surgery.

Methods

We studied 1,032 consecutive patients with invasive cancer who received lumpectomies and cavity margin (CM) assessments from January 2003 to November 2012. The following data were collected: patient age, cT stage, pT stage, grade, status of CM, lymph node status, menopausal status, ER, PR, HER-2, and Ki67, as well as the presence of extensive intraductal component (EIC) and lymphovascular invasion (LVI). A χ² test was used to compare categorical baseline characteristics. Univariate and multivariate logistic regression analyses were performed to evaluate associations between pathologic features of CM status. Kaplan-Meier actuarial cumulative rates of LR (ipsilateral in-breast) were calculated.

Results

A total of 7,884 pieces of marginal tissue were collected from 1,032 patients, and 209 patients had positive CMs. Of the patients tested, 52.3% had luminal A subtype, 14.9% were luminal B, 12.8% were luminal-HER-2, 8.1% were HER-2 enriched, and 11.8% were triple negative. Univariate analysis showed that EIC (P <0.001), LVI (P = 0.026), pN stage (N1 vs. N0: P = 0.018; N3 vs. N0: P <0.001), and luminal B (P = 0.001) and HER-2 (P <0.001) subtypes were associated with positive CMs. Multivariable analysis indicated that only EIC (P <0.001), pN stage (P = 0.003), and HER-2 subtype (P <0.001) were significantly correlated with positive CMs. On multivariable analysis, HER-2 subtype was an independent prognostic factor in LR (P = 0.031).

Conclusions

The HER-2 subtype was the predictive factor most associated with positive CMs and an independent prognostic factor for LR. This result suggests that the increased risk of LR in HER-2 breast cancer is due to an increased microscopic invasive tumor burden, which is indicated by margin status after lumpectomy.

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Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumours. Nature. 2000, 406: 747-752. 10.1038/35021093.CrossRefPubMed

Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lønning P, Børresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001, 98: 10869-10874. 10.1073/pnas.191367098.PubMedCentralCrossRefPubMed

Brenton JD, Carey LA, Ahmed AA, Caldas C: Molecular classification and molecular forecasting of breast cancer: ready for clinical application?. J Clin Oncol. 2005, 23: 7350-7360. 10.1200/JCO.2005.03.3845.CrossRefPubMed

Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lønning PE, Brown PO, Børresen-Dale AL, Botstein D: Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003, 100: 8418-8423. 10.1073/pnas.0932692100.PubMedCentralCrossRefPubMed

Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006, 295: 2492-2502. 10.1001/jama.295.21.2492.CrossRefPubMed

Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, Bellon JR, Wong JS, Smith BL, Harris JR: 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. 2008, 26: 2373-2378. 10.1200/JCO.2007.14.4287.CrossRefPubMed

Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N: Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002, 347: 1233-1241. 10.1056/NEJMoa022152.CrossRefPubMed

Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E: Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002, 347: 1227-1232. 10.1056/NEJMoa020989.CrossRefPubMed

Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R: Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2010, 378: 1707-1716.

10.

Mechera R, Viehl CT, Oertli D: Factors predicting in-breast tumor recurrence after breast-conserving surgery. Breast Cancer Res Treat. 2009, 116: 171-177. 10.1007/s10549-008-0187-y.CrossRefPubMed

11.

Komoike Y, Akiyama F, Iino Y, Ikeda T, Akashi-Tanaka S, Ohsumi S, Kusama M, Sano M, Shin E, Suemasu K, Sonoo H, Taguchi T, Nishi T, Nishimura R, Haga S, Mise K, Kinoshita T, Murakami S, Yoshimoto M, Tsukuma H, Inaji H: Ipsilateral breast tumor recurrence (IBTR) after breast-conserving treatment for early breast cancer: risk factors and impact on distant metastases. Cancer. 2006, 106: 35-41. 10.1002/cncr.21551.CrossRefPubMed

12.

Singletary SE: Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy. Am J Surg. 2002, 184: 383-393. 10.1016/S0002-9610(02)01012-7.CrossRefPubMed

13.

Freedman GM, Anderson PR, Li T, Nicolaou N: Locoregional recurrence of triple-negative breast cancer after breast-conserving surgery and radiation. Cancer. 2009, 115: 946-951. 10.1002/cncr.24094.PubMedCentralCrossRefPubMed

14.

Kim HJ, Han W, Yi OV, Shin HC, Ahn SK, Koh BS, Moon HG, You JH, Son BH, Ahn SH, Noh DY: Young age is associated with ipsilateral breast tumor recurrence after breast conserving surgery and radiation therapy in patients with HER2-positive/ER-negative subtype. Breast Cancer Res Treat. 2011, 130: 499-505. 10.1007/s10549-011-1736-3.CrossRefPubMed

15.

Park CC, Mitsumori M, Nixon A, Recht A, Connolly J, Gelman R, Silver B, Hetelekidis S, Abner A, Harris JR, Schnitt SJ: Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence. J Clin Oncol. 2000, 18: 1668-1675.PubMed

16.

Peterson ME, Schultz DJ, Reynolds C, Solin LJ: Outcomes in breast cancer patients relative to margin status after treatment with breast-conserving surgery and radiation therapy: the University of Pennsylvania experience. Int J Radiat Oncol Biol Phys. 1999, 43: 1029-1035. 10.1016/S0360-3016(98)00519-7.CrossRefPubMed

17.

Smitt MC, Nowels K, Carlson RW, Jeffrey SS: Predictors of reexcision findings and recurrence after breast conservation. Int J Radiat Oncol Biol Phys. 2003, 57: 979-985. 10.1016/S0360-3016(03)00740-5.CrossRefPubMed

18.

Fisher ER, Sass R, Fisher B, Gregorio R, Brown R, Wickerham L: Pathologic findings from the National Surgical Adjuvant Breast Project (protocol 6). II. Relation of local breast recurrence to multicentricity. Cancer. 1986, 57: 1717-1724. 10.1002/1097-0142(19860501)57:9<1717::AID-CNCR2820570902>3.0.CO;2-H.CrossRefPubMed

19.

Wright MJ, Park J, Fey JV, Park A, O’Neill A, Tan LK, Borgen PI, Cody HS, Van Zee KJ, King TA: Perpendicular inked versus tangential shaved margins in breast-conserving surgery: does the method matter?. J Am Coll Surg. 2007, 204: 541-549. 10.1016/j.jamcollsurg.2007.01.031.CrossRefPubMed

20.

Cao D, Lin C, Woo SH, Vang R, Tsangaris TN, Argani P: Separate cavity margin sampling at the time of initial breast lumpectomy significantly reduces the need for reexcisions. Am J Surg Pathol. 2005, 29: 1625-1632. 10.1097/01.pas.0000180448.08203.70.CrossRefPubMed

21.

Huston TL, Pigalarga R, Osborne MP, Tousimis E: The influence of additional surgical margins on the total specimen volume excised and the reoperative rate after breast-conserving surgery. Am J Surg. 2006, 192: 509-512. 10.1016/j.amjsurg.2006.06.021.CrossRefPubMed

22.

Tengher-Barna I, Hequet D, Reboul-Marty J, Frassati-Biaggi A, Seince N, Rodrigues-Faure A, Uzan M, Ziol M: Prevalence and predictive factors for the detection of carcinoma in cavity margin performed at the time of breast lumpectomy. Mod Pathol. 2009, 22: 299-305. 10.1038/modpathol.2008.186.CrossRefPubMed

23.

Povoski SP, Jimenez RE, Wang WP, Xu RX: Standardized and reproducible methodology for the comprehensive and systematic assessment of surgical resection margins during breast-conserving surgery for invasive breast cancer. BMC Cancer. 2009, 9: 254-10.1186/1471-2407-9-254.PubMedCentralCrossRefPubMed

24.

Chen K, Zeng Y, Jia H, Jia W, Yang H, Rao N, Song E, Cox CE, Su F: Clinical outcomes of breast-conserving surgery in patients using a modified method for cavity margin assessment. Ann Surg Oncol. 2012, 19: 3386-3394. 10.1245/s10434-012-2331-5.CrossRefPubMed

25.

Trihia H, Murray S, Price K, Gelber RD, Golouh R, Goldhirsch A, Coates AS, Collins J, Castiglione-Gertsch M, Gusterson BA: Ki-67 expression in breast carcinoma: its association with grading systems, clinical parameters, and other prognostic factors–a surrogate marker?. Cancer. 2003, 97: 1321-1331. 10.1002/cncr.11188.CrossRefPubMed

26.

De Azambuja E, Cardoso F, De Castro G, Colozza M, Mano MS, Durbecq V, Sotiriou C, Larsimont D, Piccart-Gebhart MJ, Paesmans M: Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer. 2007, 96: 1504-1513. 10.1038/sj.bjc.6603756.PubMedCentralCrossRefPubMed

27.

Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, Watson M, Davies S, Bernard PS, Parker JS, Perou CM, Ellis MJ, Nielsen TO: Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009, 101: 736-750. 10.1093/jnci/djp082.PubMedCentralCrossRefPubMed

28.

Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ: Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011, 22: 1736-1747. 10.1093/annonc/mdr304.PubMedCentralCrossRefPubMed

29.

Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, 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: Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005, 353: 1673-1684. 10.1056/NEJMoa052122.CrossRefPubMed

30.

Black MM, Speer FD: Nuclear structure in cancer tissues. Surg Gynecol Obstet. 1957, 105: 97-102.PubMed

31.

Lang JE, Mosalpuria K, Cristofanilli M, Krishnamurthy S, Reuben J, Singh B, Bedrosian I, Meric-Bernstam F, Lucci A: HER2 status predicts the presence of circulating tumor cells in patients with operable breast cancer. Breast Cancer Res Treat. 2009, 113: 501-507. 10.1007/s10549-008-9951-2.CrossRefPubMed

32.

Xenidis N, Perraki M, Kafousi M, Apostolaki S, Bolonaki I, Stathopoulou A, Kalbakis K, Androulakis N, Kouroussis C, Pallis T, Christophylakis C, Argyraki K, Lianidou ES, Stathopoulos S, Georgoulias V, Mavroudis D: Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients. J Clin Oncol. 2006, 24: 3756-3762. 10.1200/JCO.2005.04.5948.CrossRefPubMed

33.

Wiechmann L, Sampson M, Stempel M, Jacks LM, Patil SM, King T, Morrow M: Presenting features of breast cancer differ by molecular subtype. Ann Surg Oncol. 2009, 16: 2705-2710. 10.1245/s10434-009-0606-2.CrossRefPubMed

34.

Albert JM, Gonzalez-Angulo AM, Guray M, Sahin A, Strom EA, Tereffe W, Woodward WA, Tucker SL, Hunt KK, Hortobagyi GN, Buchholz TA: Estrogen/progesterone receptor negativity and HER2 positivity predict locoregional recurrence in patients with T1a, bN0 breast cancer. Int J Radiat Oncol Biol Phys. 2010, 77: 1296-1302. 10.1016/j.ijrobp.2009.12.011.CrossRefPubMed

35.

Cancello G, Maisonneuve P, Rotmensz N, Viale G, Mastropasqua MG, Pruneri G, Veronesi P, Torrisi R, Montagna E, Luini A, Intra M, Gentilini O, Ghisini R, Goldhirsch A, Colleoni M: Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer. Ann Oncol. 2010, 21: 1974-1981. 10.1093/annonc/mdq072.CrossRefPubMed

36.

Arvold ND, Taghian AG, Niemierko A, Abi Raad RF, Sreedhara M, Nguyen PL, Bellon JR, Wong JS, Smith BL, Harris JR: Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. J Clin Oncol. 2011, 29: 3885-3891. 10.1200/JCO.2011.36.1105.PubMedCentralCrossRefPubMed

37.

Hattangadi-Gluth JA, Wo JY, Nguyen PL, Abi Raad RF, Sreedhara M, Niemierko A, Freer PE, Georgian-Smith D, Bellon JR, Wong JS, Smith BL, Harris JR, Taghian AG: Basal subtype of invasive breast cancer is associated with a higher risk of true recurrence after conventional breast-conserving therapy. Int J Radiat Oncol Biol Phys. 2012, 82: 1185-1191. 10.1016/j.ijrobp.2011.02.061.CrossRefPubMed

38.

Lin NU, Vanderplas A, Hughes ME, Theriault RL, Edge SB, Wong YN, Blayney DW, Niland JC, Winer EP, Weeks JC: Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer. 2012, 118: 5463-5472. 10.1002/cncr.27581.PubMedCentralCrossRefPubMed

39.

Sioshansi S, Ehdaivand S, Cramer C, Lomme MM, Price LL, Wazer DE: Triple negative breast cancer is associated with an increased risk of residual invasive carcinoma after lumpectomy. Cancer. 2012, 118: 3893-3898. 10.1002/cncr.27376.CrossRefPubMed

40.

Wazer DE, Schmidt-Ullrich RK, Schmid CH, Ruthazer R, Kramer B, Safaii H, Graham R: The value of breast lumpectomy margin assessment as a predictor of residual tumor burden. Int J Radiat Oncol Biol Phys. 1997, 38: 291-299. 10.1016/S0360-3016(97)82498-4.CrossRefPubMed

41.

Beck NE, Bradburn MJ, Vincenti AC, Rainsbury RM: Detection of residual disease following breast-conserving surgery. Br J Surg. 1998, 85: 1273-1276. 10.1046/j.1365-2168.1998.00876.x.CrossRefPubMed

42.

Barthelmes L, Al Awa A, Crawford DJ: Effect of cavity margin shavings to ensure completeness of excision on local recurrence rates following breast conserving surgery. Eur J Surg Oncol. 2003, 29: 644-648. 10.1016/S0748-7983(03)00122-7.CrossRefPubMed

43.

Hewes JC, Imkampe A, Haji A, Bates T: Importance of routine cavity sampling in breast conservation surgery. Br J Surg. 2009, 96: 47-53. 10.1002/bjs.6435.CrossRefPubMed

Title: HER-2 positive breast cancer is associated with an increased risk of positive cavity margins after initial lumpectomy
Authors: Haixia Jia
Weijuan Jia
Yaping Yang
Shunrong Li
Huiyi Feng
Jieqiong Liu
Nanyan Rao
Liang Jin
Jiannan Wu
Ru Gu
Liling Zhu
Kai Chen
Heran Deng
Yunjie Zeng
Qiang Liu
Erwei Song
Fengxi Su
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: World Journal of Surgical Oncology / Issue 1/2014
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/1477-7819-12-289

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

HER-2 positive breast cancer is associated with an increased risk of positive cavity margins after initial lumpectomy

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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