Publications by authors named "Ian Kunkler"

Background: There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low risk cancers where RT will not further reduce recurrence rates.

Methods: An individual participant data meta-analysis was performed in 623 cases of node-negative ER+/HER2-negative early breast cancer enrolled in three RT randomized trials for whom primary tumor material was available for analysis.

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Background: Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial.

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This editorial discusses the evolving landscape of early-stage breast cancer treatment, emphasizing the need to tailor therapies based on disease biology and genomic approaches. The focus is on the reconsideration of postoperative radiation therapy (RT) for older patients with low-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Recent trials show modest long-term local recurrence rates with the omission of RT after BCS in certain cases, challenging the traditional approach.

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Article Synopsis
  • A phase 3 randomized trial was conducted to explore the effects of omitting radiotherapy in older women (65+) with hormone receptor-positive early breast cancer after breast-conserving surgery.
  • Of the 1326 participating women, those who did not receive radiotherapy had a significantly higher local breast cancer recurrence rate (9.5%) compared to those who did (0.9%), but overall survival rates were nearly the same in both groups (around 80.8%).
  • The findings suggest that while omitting radiotherapy may lead to higher local recurrences, it does not impact distant recurrence or overall survival for these patients on adjuvant endocrine therapy.
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Article Synopsis
  • - The study aimed to determine if adding a tumour bed boost after whole breast irradiation (WBI) improves outcomes for women with non-low-risk ductal carcinoma in situ (DCIS) post-surgery, focusing on local recurrence rates.
  • - Conducted as a phase 3 trial across 11 countries, 1,608 women participated, receiving either no boost or a boost after either conventional or hypofractionated WBI, with 6.6 years of median follow-up.
  • - Results showed the boost group had a significantly lower local recurrence rate (97.1%) compared to the no-boost group (92.7%), although the boost also led to higher reports of breast pain.
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Breast cancer in older patients presents an increasing health care challenge. Hypofractionated dose schedules of 15/16 daily fractions of postoperative radiotherapy over 3/3.5 weeks have been established in clinical trials with long term follow up as safe and effective and become the standard of care after breast conserving therapy for most older patients.

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Combined chemoradiotherapy is the standard of care for locally advanced solid tumours. However, systemic toxicity may limit the delivery of planned chemotherapy. New approaches such as radiation-induced prodrug activation might diminish systemic toxicity, while retaining anticancer benefit.

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For older patients with clinically lymph node-negative breast cancer who have estrogen receptor-positive tumors and are treated with tamoxifen, randomized trials comparing axillary lymph node dissection (ALND) versus no ALND show that the omission of ALND improves patient quality of life and has no adverse effects on mortality. These results have served to justify sentinel node biopsy (SNB) omission in selected older patients with breast cancer. More recently, clinical trials were launched to assess SNB omission in younger patients, with recurrence and survival as the primary outcomes of interest.

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Purpose Of Review: We review the role of postmastectomy radiotherapy (PMRT) in the management of patients with early breast cancer.

Recent Findings: PMRT in patients with 4 or more involved axillary lymph nodes is the current standard of care but the indications for PMRT in patients with 1-3 involved nodes remain controversial. The Early Breast Cancer Trialists' Collaborative Group meta-analysis of randomised trials of PMRT provides the most comprehensive level 1 evidence base.

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Radiotherapy (RT) is an important treatment modality for the local control of breast cancer (BC). Unfortunately, not all patients that receive RT will obtain a therapeutic benefit, as cancer cells that either possess intrinsic radioresistance or develop resistance during treatment can reduce its efficacy. For RT treatment regimens to become personalised, there is a need to identify biomarkers that can predict and/or monitor a tumour's response to radiation.

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Breast cancer is increasingly prevalent in older adults and is a substantial part of routine oncology practice. However, management of breast cancer in this population is challenging because the disease is highly heterogeneous and there is insufficient evidence specific to older adults. Decision making should not be driven by age alone but should involve geriatric assessments plus careful consideration of life expectancy, competing risks of mortality, and patient preferences.

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Radiotherapy remains an important treatment modality in nearly two thirds of all cancers, including the primary curative or palliative treatment of breast cancer. Unfortunately, largely due to tumor heterogeneity, tumor radiotherapy response rates can vary significantly, even between patients diagnosed with the same tumor type. Although in recent years significant technological advances have been made in the way radiation can be precisely delivered to tumors, it is proving more difficult to personalize radiotherapy regimens based on cancer biology.

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Background: BIG 3-07/TROG 07.01 is an international, multicentre, randomised, controlled, phase 3 trial evaluating tumour bed boost and hypofractionation in patients with non-low-risk ductal carcinoma in situ following breast-conserving surgery and whole breast radiotherapy. Here, we report the effects of diagnosis and treatment on health-related quality of life (HRQOL) at 2 years.

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Dysregulation of cellular pH is frequent in solid tumours and provides potential opportunities for therapeutic intervention. The acidic microenvironment within a tumour can promote migration, invasion and metastasis of cancer cells through a variety of mechanisms. Pathways associated with the control of intracellular pH that are under consideration for intervention include carbonic anhydrase IX, the monocarboxylate transporters (MCT, MCT1 and MCT4), the vacuolar-type H-ATPase proton pump, and the sodium-hydrogen exchanger 1.

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Purpose: To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast.

Materials And Methods: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/- TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres.

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Carbonic anhydrase inhibitors (CAIs) of the sulfonamide, sulfamate and coumarin classes bearing the phenylureido tail found in the clinically used drug Sorafenib, a multikinase inhibitor actually used for the management of hepatocellular carcinomas, are reported. All compounds were assayed on human (h) CA isoforms I, II, VII and IX, involved in various pathologies. Among the sulfonamides, several compounds were selective for inhibiting hCA IX, with K values in the low nanomolar ranges (i.

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Recent advances in the fields of electronics and microfabrication techniques have led to the development of implantable medical devices for use within the field of precision medicine. Monitoring visceral surface tissue O tension () by means of an implantable sensor is potentially useful in many clinical situations, including the perioperative management of patients undergoing intestinal resection and anastomosis. This concept could provide a means by which treatment could be tailored to individual patients.

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Background: Radiotherapy plays an important role in the multimodal treatment of breast cancer. The response of a breast tumour to radiation depends not only on its innate radiosensitivity but also on tumour repopulation by cells that have developed radioresistance. Development of effective cancer treatments will require further molecular dissection of the processes that contribute to resistance.

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The immense costs in both financial terms and preclinical research effort that occur in the development of anticancer drugs are unfortunately not matched by a substantial increase in improved clinical therapies due to the high rate of failure during clinical trials. This may be due to issues with toxicity or lack of clinical effectiveness when the drug is evaluated in patients. Currently, much cancer research is driven by the need to develop therapies that can exploit cancer cell adaptations to conditions in the tumor microenvironment such as acidosis and hypoxia, the requirement for more-specific, targeted treatments, or the exploitation of 'precision medicine' that can target known genomic changes in patient DNA.

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Aims: This study aimed to explore breast cancer patients' understanding and acceptability of implanted biosensors (BS) within the primary tumour to personalise adjuvant radiotherapy, and to determine optimal design and number of BS, and evaluate potential clinical benefits as well as concerns about tolerance, toxicity, dwell time, and confidentiality of data.

Patients And Methods: A total of 32 patients treated by surgery (29 breast conserving, 3 mastectomy), postoperative radiotherapy and systemic therapy for early breast cancer, were recruited from a posttreatment radiotherapy clinic at a cancer centre. Patients participated in semistructured interviews.

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Real-time monitoring of tumor microenvironment parameters using an implanted biosensor could provide valuable information on the dynamic nature of a tumor's biology and its response to treatment. However, following implantation biosensors may lose functionality due to biofouling caused by the foreign body response (FBR). This study developed a novel tumor xenograft model to evaluate the potential of six biomaterials (silicon dioxide, silicon nitride, Parylene-C, Nafion, biocompatible EPOTEK epoxy resin, and platinum) to trigger a FBR when implanted into a solid tumor.

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