The Effect of Adjuvant Trastuzumab on Locoregional Recurrence of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Treated with Mastectomy

Lanning, Ryan M.; Morrow, Monica; Riaz, Nadeem; McArthur, Heather L.; Dang, Chau T.; Moo, Tracy-Ann; El‐Tamer, Mahmoud; Krause, Kate; Siu, Chun; Hsu, Meier; Zhang, Zhigang; Pei, Xin; McCormick, Beryl; Powell, Simon N.; Ho, Alice Y.

doi:10.1245/s10434-014-4321-2

Cited by 29 publications

(21 citation statements)

References 25 publications

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“…In patients with HER2-over-expressing tumors, different researches have shown cellular and/or humoral immune responses against HER2 associated with a lower tumor development at early stages of the disease (Ladjemi et al, 2010;Xia et al, 2013;Lanning et al, 2015). and for one of the mechanisms, HER2-mediated signaling effects cyclin E expression (Dong et al, 2014), which in turn deregulates the cell cycle in early high-risk breast cancer (Mittendorf et al, 2010).…”

Section: Mechanism Of Her2mentioning

confidence: 99%

“…Also, HER2 over-expression was associated with locoregional recurrence (LRR) in the pre-adjuvant trastuzumab era (Lanning et al, 2015). trastuzumab may modulate LRR risk in HER2 (+) breast cancer patients.…”

Section: Other Associated Micromoleculesmentioning

confidence: 99%

“…And in predominantly stage I HER2-positive breast cancer, treatment with adjuvant paclitaxel plus trastuzumab was associated with a risk of early recurrence of about 2% (Tolaney et al, 2015). Also, the good outcomes are limited regarding its impact on locoregional recurrence (LRR) in patients undergoing mastectomy, particularly those receiving (post-mastectomy radiation) PMRT (Lanning et al, 2015). …”

Section: Trastuzumabmentioning

confidence: 99%

See 2 more Smart Citations

Recent Progress in HER2 Associated Breast Cancer

Wang¹,

Lei²,

Mei³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Section: Mechanism Of Her2mentioning

confidence: 99%

Section: Other Associated Micromoleculesmentioning

confidence: 99%

Section: Trastuzumabmentioning

confidence: 99%

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Recent Progress in HER2 Associated Breast Cancer

Wang¹,

Lei²,

Mei³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…32,33 However, a major concern was the possible increase in cardiotoxicity by the combination of irradiation and trastuzumab. In a review article, 34 Chien and colleagues described the interaction between trastuzumab and anthracyclins and explained why this combination has led to an increase in myocardial injury.…”

Section: Trastuzumab and Radiotherapymentioning

confidence: 99%

Lessons Learned in Breast-Conserving Therapy

Scholten¹,

Bartelink²

2015

Breast Diseases: A Year Book Quarterly

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“…9 Recent, retrospective, single-institution data support this benefit and have shown significant improvement in LRFS after both mastectomy and BCT with trastuzumab therapy. 10,11 Moreover, an expanded use of trastuzumab-based systemic therapy has been prompted by multiple retrospective studies showing a higher distant recurrence risk for HER2-positive T1b/c stage I cancers than estimated from conventional staging. 12 Consequently, guidelines now recommend trastuzumab for most HER2-positive lesions [5 mm and many are considering treatment for cancers below this threshold as well.…”

mentioning

confidence: 99%

Implications of HER2-Targeted Therapy on Extent of Surgery for Early-Stage Breast Cancer

2015

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Over the past three decades, our understanding of the molecular underpinnings of breast cancer has improved at an unprecedented rate. During this same period, mammographic screening has led to a doubling in the incidence of early-stage breast cancers and an eightfold increase in the incidence of DCIS.1 This has led to tremendous interest in understanding the biology of early-stage breast cancers, including DCIS and tailoring both local and systemic treatment to the molecular, histologic, and morphologic features that drive tumor behavior.HER2, a transmembrane receptor with tyrosine kinase activity, is overexpressed at the mRNA and/or protein level in approximately 20 % of early-stage breast cancer. Before the widespread use of HER2-targeted therapy, primarily with the monoclonal antibody trastuzumab, overexpression of HER2 was clearly associated with high recurrence rates and increased mortality.2 The HER2-positive subtype confers a high risk of local failure independent of whether patients were treated with breast-conserving therapy (BCT) or mastectomy. An extensive analysis of 10-year local recurrence-free survival (LRFS) showed that the HER2 subtype had a LRFS of 83 % after mastectomy and 79 % after BCT compared with 92 % for both mastectomy and BCT in the Luminal A subtype.3 Important to note, however, is that this study reported on patients diagnosed from 1986 to 1992, before use of trastuzumab.In the preceding article, Dr. Tot examined 203 consecutive cases of newly diagnosed invasive breast carcinomas measuring \10 mm in size during the period 2007-2013 at a single institution, including 23 cases of HER2-positive disease. A validation cohort of 80 cases from 1996 to 1998 also was analyzed. In both sets of samples, HER2-positive breast cancers were found to be more often associated with a higher component of diffuse DCIS around the invasive tumor (p \ 0.0001), more likely to be of higher grade (p = 0.0004), and have lymphovascular invasion (p = 0.0026) compared with tumors lacking HER2 overexpression. Although no multivariable analysis or recurrence data were provided, the author postulates a causal role of extensive DCIS for HER2-positive breast cancer recurrence.The presence of an extensive intraductal component (EIC) has been recognized to be associated with a higher local recurrence rate following BCT, long before genomic subtyping of tumors. 4,5 However, the impact of EIC on local outcomes has been shown to be largely abrogated when free margins are achieved and when adjusted for age at diagnosis. [5][6][7] In the recently published ASCO/ASTRO guidelines, an extensive meta-analysis failed to support that larger margins were indicated for any tumor phenotype, including the HER2-positive subtype.8 Moreover, HER2-positive breast cancers are biologically more aggressive independent of EIC, as is well demonstrated in Dr. Tot's own data. In the absence of outcomes in Dr. Tot's study, it is difficult to recommend any change in surgical treatment based on these observations alone, but an awareness of the asso...

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The Effect of Adjuvant Trastuzumab on Locoregional Recurrence of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Treated with Mastectomy

Cited by 29 publications

References 25 publications

Recent Progress in HER2 Associated Breast Cancer

Recent Progress in HER2 Associated Breast Cancer

Lessons Learned in Breast-Conserving Therapy

Implications of HER2-Targeted Therapy on Extent of Surgery for Early-Stage Breast Cancer

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