Modulating the Radiation Response for Improved Outcomes in Breast Cancer

Pesch, Andrea M.; Pierce, Lori J.; Speers, Corey

doi:10.1200/po.20.00297

Cited by 7 publications

(9 citation statements)

References 176 publications

(189 reference statements)

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“…While in this study we demonstrate that AR expression may be influencing the efficacy of ER inhibitors in modulating radiosensitisation in AR+/ER+ breast cancer cells, future studies are necessary to understand why ER-targeting therapies may be effective for the radiosensitisation in some preclinical ER+ breast cancer models but not others. This may be due to the expression of additional biomarkers that can impact radiosensitivity including HER2 and EGFR [ 49 – 52 ], PI3K/mTOR [ 53 , 54 ] and PARP [ 55 – 57 ], among others. While preclinical studies are useful to start interrogating these questions using models that have been studied extensively, translation of these findings into the clinic brings additional variabilities including, but not limited to, individual patient characteristics, adherence to treatment, as well as other concurrent therapies.…”

Section: Discussionmentioning

confidence: 99%

Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer

et al. 2022

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Purpose Radiation therapy (RT) and hormone receptor (HR) inhibition are used for the treatment of HR-positive breast cancers; however, little is known about the interaction of the androgen receptor (AR) and estrogen receptor (ER) in response to RT in AR-positive, ER-positive (AR+/ER+) breast cancers. Here we assessed radiosensitisation of AR+/ER+ cell lines using pharmacologic or genetic inhibition/degradation of AR and/or ER. Methods Radiosensitisation was assessed with AR antagonists (enzalutamide, apalutamide, darolutamide, seviteronel, ARD-61), ER antagonists (tamoxifen, fulvestrant) or using knockout of AR. Results Treatment with AR antagonists or ER antagonists in combination with RT did not result in radiosensitisation changes (radiation enhancement ratios [rER]: 0.76–1.21). Fulvestrant treatment provided significant radiosensitisation of CAMA-1 and BT-474 cells (rER: 1.06–2.0) but not ZR-75-1 cells (rER: 0.9–1.11). Combining tamoxifen with enzalutamide did not alter radiosensitivity using a 1 h or 1-week pretreatment (rER: 0.95–1.14). Radiosensitivity was unchanged in AR knockout compared to Cas9 cells (rER: 1.07 ± 0.11), and no additional radiosensitisation was achieved with tamoxifen or fulvestrant compared to Cas9 cells (rER: 0.84–1.19). Conclusion While radiosensitising in AR + TNBC, AR inhibition does not modulate radiation sensitivity in AR+/ER+ breast cancer. The efficacy of ER antagonists in combination with RT may also be dependent on AR expression.

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Section: Discussionmentioning

confidence: 99%

Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer

et al. 2022

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“…The review by Pesch et al [56] includes ongoing trials of concurrent radiation and radiation response modulators including PAPR inhibitors and immunotherapy that are not the subject of our manuscript. Recent phase II trials evaluating pre-operative dual modality chemo-radiation therapy for patients with TNBC are included in Table 3.…”

Section: Discussionmentioning

confidence: 99%

Concurrent Chemo-radiation As a Means of Achieving Pathologic Complete Response in Triple Negative Breast Cancer

Shafaee

Makawita

Ellis

et al. 2022

Clinical Breast Cancer

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“…Clinical radiotherapy involves the delivery of fractionated doses of ionizing radiation to the affected cancerous breast tissue while sparing the surrounding benign tissues. This results in targeted disruption of tumor cells through induction of DNA damage, alterations in the cell cycle, and ultimately cancer cell death ( 138 – 140 ). Multiple randomized clinical trials have effectively established that radiotherapy reduces local recurrence in both invasive and noninvasive breast cancers, in addition to reducing the risk of breast cancer death ( 141 – 143 ).…”

Section: Introductionmentioning

confidence: 99%

“…The combination of chemotherapy, radiotherapy, and surgery is the standard of care for breast cancer treatment, while numerous studies support the therapeutic potential of combining radiotherapy with chemotherapy for treating breast cancer patients. The evidence supporting the integration of radiotherapy with chemotherapy has been more extensively reviewed elsewhere ( 140 , 195 , 196 ). Importantly, many chemotherapies function by inducing DNA damage, consequently resulting in synergistic effects when combined with radiotherapy in the preclinical and clinical setting ( 140 , 197 ).…”

Section: Introductionmentioning

confidence: 99%

“…The evidence supporting the integration of radiotherapy with chemotherapy has been more extensively reviewed elsewhere ( 140 , 195 , 196 ). Importantly, many chemotherapies function by inducing DNA damage, consequently resulting in synergistic effects when combined with radiotherapy in the preclinical and clinical setting ( 140 , 197 ). Cytotoxic chemotherapeutic agents—such as platinums, taxanes, and antimetabolites—have been found to promote synergistic, radiosensitizing effects in breast cancer ( 198 ).…”

Section: Introductionmentioning

confidence: 99%

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Updates in combined approaches of radiotherapy and immune checkpoint inhibitors for the treatment of breast cancer

et al. 2022

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Breast cancer is the most prevalent non-skin cancer diagnosed in females and developing novel therapeutic strategies to improve patient outcomes is crucial. The immune system plays an integral role in the body’s response to breast cancer and modulating this immune response through immunotherapy is a promising therapeutic option. Although immune checkpoint inhibitors were recently approved for the treatment of breast cancer patients, not all patients respond to immune checkpoint inhibitors as a monotherapy, highlighting the need to better understand the biology underlying patient response. Additionally, as radiotherapy is a critical component of breast cancer treatment, understanding the interplay of radiation and immune checkpoint inhibitors will be vital as recent studies suggest that combined therapies may induce synergistic effects in preclinical models of breast cancer. This review will discuss the mechanisms supporting combined approaches with radiotherapy and immune checkpoint inhibitors for the treatment of breast cancer. Moreover, this review will analyze the current clinical trials examining combined approaches of radiotherapy, immunotherapy, chemotherapy, and targeted therapy. Finally, this review will evaluate data regarding treatment tolerance and potential biomarkers for these emerging therapies aimed at improving breast cancer outcomes.

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Modulating the Radiation Response for Improved Outcomes in Breast Cancer

Abstract: Author affiliations and support information (if applicable) appear at the end of this article.

Cited by 7 publications

References 176 publications

Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer

Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer

Concurrent Chemo-radiation As a Means of Achieving Pathologic Complete Response in Triple Negative Breast Cancer

Updates in combined approaches of radiotherapy and immune checkpoint inhibitors for the treatment of breast cancer

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