Breast Cancer Subtype and Distant Recurrence after Ipsilateral Breast Tumor Recurrence

Ishitobi, Makoto; Okumura, Yasuhiro; Arima, Nobuyuki; Yoshida, Atsushi; Nakatsukasa, Katsuhiko; Iwase, Takuji; Shien, Tadahiko; Masuda, Norikazu; Tanaka, Satoru; Tanabe, Masahiko; Tanaka, Takehiro; Komoike, Yoshifumi; Taguchi, Tetsuya; Nishimura, Reiki; Inaji, Hideo

doi:10.1245/s10434-012-2825-1

Cited by 15 publications

(18 citation statements)

References 34 publications

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“…In our study, the 5-year DDFS rate was 74.4% in patients with late IBTR. This DDFS rate is comparable with the rates in other reports (range 68-80.3%) [6,13,16]. Therefore, it is clinically important to assess risk factors after late IBTR.…”

Section: Discussionsupporting

confidence: 88%

“…Several reports have demonstrated that patients with late IBTR have a better prognosis than those with early IBTR [3,4,5,6,8,9,10,11,12,13,14,15,16]. However, distant recurrence after late IBTR is not rare.…”

Section: Discussionmentioning

confidence: 99%

“…According to these studies, the time interval from initial surgery to IBTR (disease-free interval) was one of the most important predictors of disease recurrence after IBTR [3,4,5,6,8,9,10,11,12,13,14,15,16]. Patients with IBTR >5 years after breast-conserving surgery have a better prognosis than patients with earlier IBTR [8,13,15,16]. However, it is not rare for patients with IBTR >5 years after initial surgery to develop systemic recurrence [6,13,16].…”

Section: Introductionmentioning

confidence: 99%

“…Patients with IBTR >5 years after breast-conserving surgery have a better prognosis than patients with earlier IBTR [8,13,15,16]. However, it is not rare for patients with IBTR >5 years after initial surgery to develop systemic recurrence [6,13,16]. Therefore, it is important to estimate the risk of distant recurrence for such patients.…”

Section: Introductionmentioning

confidence: 99%

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Distant Recurrence Risk after Late Ipsilateral Breast Tumor Recurrence: Results of a Retrospective, Single-Institution Study

Ishitobi

Okuno²,

Kittaka³

et al. 2015

Oncology

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Objectives: There is limited information regarding risk factors for distant recurrence in patients with late ipsilateral breast tumor recurrence (IBTR). Methods: Late IBTR was defined as IBTR occurring >5 years after the initial surgery. Seventy-eight patients with late IBTR were reviewed to examine the risk factors of distant recurrence. Results: The negative estrogen receptor and positive HER2 statuses of IBTR were significantly correlated with poorer distant disease-free survival (p = 0.03 and 0.02, respectively). Multivariate analyses demonstrated that the HER2 status of IBTR was an independent predictive factor of distant recurrence (p = 0.04). Conclusions: The results of our retrospective, single-institution study revealed that the HER2 status of IBTR was an independent predictive factor of distant recurrence in patients with late IBTR.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Distant Recurrence Risk after Late Ipsilateral Breast Tumor Recurrence: Results of a Retrospective, Single-Institution Study

Ishitobi

Okuno²,

Kittaka³

et al. 2015

Oncology

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“…HER2 expression in ERC breast cancers characterises a dominant form of the 'luminal B' molecular subtype and, compared with ERC/HER2K (luminal A) tumours, these tumours tend to exhibit reduced disease-free survival (Ishitobi et al 2013) or increased recurrence rates (Millar et al 2009) and an approximately twofold increased adjusted risk of breast cancer mortality (Haque et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Targeting focal adhesion kinase in ER+/HER2+ breast cancer improves trastuzumab response

Lazaro¹,

Smith

Goddard

et al. 2013

Endocrine-Related Cancer

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The HER2 transmembrane receptor is a well-characterised predictive marker for trastuzumab benefit and may be associated with decreased benefit from endocrine therapy use. Despite the clinical effectiveness of anti-HER2 agents in such cases, resistance represents a significant limiting factor. Focal adhesion kinase (FAK) plays an important role in HER2 signalling, mediating downstream Akt activation in addition to HER2 cross talk with other growth factor receptors. In this study, we investigated the therapeutic potential of FAK in oestrogen receptor-positive (ERC)/HER2C breast cancer using the novel FAK-specific inhibitor PF4554878 ('PF878'). The activation of the FAK/HER2 signalling pathway was assessed in ERC/HER2K (MCF7 and T47D) and ERC/HER2C (BT-474 and MDAMB361) breast cancer cells in the presence or absence of PF878 and PF878Gtrastuzumab. The effects of PF878 on cell growth as a monotherapy and in combination with trastuzumab were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Coulter counting with isobologram analysis to determine synergy/additive effects. FAK activation (at Y861 but not at Y397) was highest in ERC/HER2C cells, which also demonstrated the greatest sensitivity to PF878. As a monotherapy, PF878 prevented heregulin-induced MDA361 cell migration, but had no significant effect on cell growth. The treatment of ERC/HER2C cells with PF878 and trastuzumab in combination resulted in the synergistic inhibition of cell proliferation. Underlying this was an abrogation of Akt activity and increased poly(ADP-ribose) polymerase cleavage, effects that were greatest in trastuzumab-refractory MDA361 cells. Collectively, these data support a role for FAK in ERC/HER2C breast cancer, where its targeting has the potential to improve trastuzumab response. This is particularly important in the context of ERC/HER2C, trastuzumab-refractory disease, where FAK inhibition may present an important strategy to restore trastuzumab sensitivity.

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Regional lymphatic recurrence after salvage surgery for ipsilateral breast tumor recurrence of breast cancer without local treatment for regional lymphatic basin

Ishitobi

Matsushita

Nakayama

et al. 2014

Journal of Surgical Oncology

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Breast Cancer Subtype and Distant Recurrence after Ipsilateral Breast Tumor Recurrence

Abstract: Our study suggests that breast cancer subtype based on immunohistochemical staining predicts the outcomes of patients with IBTR. Further analyses are needed (UMIN-CTR number UMIN000008136).

Cited by 15 publications

References 34 publications

Distant Recurrence Risk after Late Ipsilateral Breast Tumor Recurrence: Results of a Retrospective, Single-Institution Study

Distant Recurrence Risk after Late Ipsilateral Breast Tumor Recurrence: Results of a Retrospective, Single-Institution Study

Targeting focal adhesion kinase in ER+/HER2+ breast cancer improves trastuzumab response

Regional lymphatic recurrence after salvage surgery for ipsilateral breast tumor recurrence of breast cancer without local treatment for regional lymphatic basin

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