Breast Cancer Biology: Clinical Implications for Breast Radiation Therapy

Horton, Janet K.; Jagsi, Reshma; Woodward, Wendy A.; Ho, Alice Y.

doi:10.1016/j.ijrobp.2017.08.025

Cited by 53 publications

(29 citation statements)

References 89 publications

(109 reference statements)

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“…It is important to note that, although patients with TNG BC have inferior 10-year locoregional outcomes compared with other subtypes ( 10 , 14 – 16 ), the data in the literature have no specific surgical implications, because the risk of LRR is unaltered, regardless of whether breast conservation or mastectomy is elected (Figure 1 A). This reinforces the concept that the prognosis of TNG and HER2-positive BC are mainly driven by the biology of the disease, rather than by the extent of the surgery ( 17 ).…”

Section: Salvage Therapy For Local Recurrence After Initial Conservatsupporting

confidence: 84%

“…(B) Algorithm for management of BC regional recurrences. Local recurrences: prognosis of TNG and HER2-positive of primary or recurrent BC are mainly driven by the biology of the disease, rather than by the extent of the surgery ( 17 , 51 ). RT after salvage surgery: HER2 positive are more radioresistant than luminal BC ( 42 , 43 ) and need more aggressive therapy.…”

Section: Salvage Therapy For Local Recurrence After Initial Conservatmentioning

confidence: 99%

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Local and Regional Breast Cancer Recurrences: Salvage Therapy Options in the New Era of Molecular Subtypes

et al. 2018

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Isolated local or regional recurrence of breast cancer (BC) leads to an increased risk of metastases and decreased survival. Ipsilateral breast recurrence can occur at the initial tumor bed or in another quadrant of the breast. Depending on tumor patterns and molecular subtypes, the risk and time to onset of metastatic recurrence differs. HER2-positive and triple-negative (TNG) BC have a risk of locoregional relapse between six and eight times than luminal A. Thus, the management of local and locoregional relapses must take into account the prognostic factors for metastatic disease development. It is important to personalize the overall management, including or not systemic treatment according to the metastatic risk. All isolated recurrence cases should be treated with curative intent. Complete surgical resection is recommended whenever possible. Patients who did not receive postoperative irradiation during their initial management should receive full-dose radiotherapy to the chest wall and to the regional lymph nodes if appropriate. Overall, total mastectomy is the “gold standard” among patients who were previously treated by conservative surgery followed by radiation therapy. In terms of systemic therapy, the benefits of additional treatments are not conclusively proven in cases of isolated recurrence. The beneficial role of chemotherapy has been reported in at least one randomized trial, while endocrine therapy and anti-HER2 are common practice. This review will discuss salvage treatment options of local and locoregional recurrences in the new era of BC molecular subtypes.

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Section: Salvage Therapy For Local Recurrence After Initial Conservatsupporting

confidence: 84%

Section: Salvage Therapy For Local Recurrence After Initial Conservatmentioning

confidence: 99%

Local and Regional Breast Cancer Recurrences: Salvage Therapy Options in the New Era of Molecular Subtypes

et al. 2018

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“…Radiation therapy (RT) remains a mainstay therapy for patients with BC and has been shown to not only reduce local recurrence (LR) but improve overall survival for these patients (2). Although RT is effective for many patients with BC, a significant proportion of them, especially those with basal-like BC, continue to have high rates of LR and poor overall survival, suggesting that RT is not as effective in those patient populations (3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

TTK inhibition radiosensitizes basal-like breast cancer through impaired homologous recombination

Chandler¹,

Moubadder²,

Ritter³

et al. 2020

Journal of Clinical Investigation

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tumor volume was calculated using the equation: volume = (length × width 2) × π/6. Additive and synergistic effects were calculated using the FTV method as previously described (59, 60). Study approval. The protocols used in this study were approved by the IACUC of the University of Michigan. Statistics. Statistical analyses were performed using GraphPad Prism 7.0 (GraphPad Software). A log-rank (Mantel-Cox) test was used for survival curve analyses. One-way ANOVA was performed for BC subtype analysis. A 2-sided Student's t test and 1-way ANOVA with Dunnett's multiple comparisons test were used for in vitro statistical analyses. A 1-way ANOVA with Dunnett's multiple comparisons test and a log-rank (Mantel-Cox) test were used for in vivo analyses. A P value of 0.05 or less was considered statistically significant.

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“…Radiation therapy (RT) is a treatment method that locally destroys cancer cells using high energy photons or particles. Many preclinical and clinical studies have been performed to determine RT response in different molecular subtypes of breast cancer, and sensitivity to radiation seems to be higher in hormone-positive tumors as compared to that of HER2-type or TNBC [6]. To enhance the effects of RT in TNBC, several agents have been investigated in preclinical studies [5,7].…”

Section: Introductionmentioning

confidence: 99%

Checkpoint Kinase 1 (CHK1) Inhibition Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Proton Irradiation via Rad51 Downregulation

Choi

Cho

Park

et al. 2020

IJMS

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Due to a superior dose conformity to the target, proton beam therapy (PBT) continues to rise in popularity. Recently, considerable efforts have been directed toward discovering treatment options for use in combination with PBT. This study aimed to investigate the targeting of checkpoint kinase 1 (CHK1), a critical player regulating the G2/M checkpoint, as a promising strategy to potentiate PBT in human triple-negative breast cancer (TNBC) cells. Protons induced cell-cycle arrest at the G2/M checkpoint more readily in response to increased CHK1 activation than X-rays. A clonogenic survival assay revealed that CHK1 inhibition using PF-477736 or small interfering RNA (siRNA) enhanced the sensitivity toward protons to a greater extent than toward X-rays. Western blotting demonstrated that PF-477736 treatment in the background of proton irradiation increased the pro-apoptotic signaling, which was further supported by flow cytometry using annexin V. Immunofluorescence revealed that proton-induced DNA double-strand breaks (DSBs) were further enhanced by PF-477736, which was linked to the downregulation of Rad51, essential for the homologous recombination repair of DSBs. Direct inactivation of Rad51 resulted in enhanced proton sensitization. Collectively, these data suggest that targeting CHK1 may be a promising approach for improving PBT efficacy in the treatment of TNBC.

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Breast Cancer Biology: Clinical Implications for Breast Radiation Therapy

Cited by 53 publications

References 89 publications

Local and Regional Breast Cancer Recurrences: Salvage Therapy Options in the New Era of Molecular Subtypes

Local and Regional Breast Cancer Recurrences: Salvage Therapy Options in the New Era of Molecular Subtypes

TTK inhibition radiosensitizes basal-like breast cancer through impaired homologous recombination

Checkpoint Kinase 1 (CHK1) Inhibition Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Proton Irradiation via Rad51 Downregulation

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