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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. Organic azides have recently been shown to be reduced and activated under hypoxic conditions with clinically relevant doses of radiotherapy, uncaging pazopanib and doxorubicin in preclinical models with similar efficacy as the drug, but lower systemic toxicity. This approach may be relevant to the chemoradiation of glioblastoma and other solid tumours and offers potential for switching on drug delivery from implanted devices. The inclusion of reporters to confirm drug activation, avoidance of off-target effects and synchronisation of irradiation with optimal intratumoral drug concentration will be critical. Further preclinical validation studies of this approach should be encouraged., (© 2022. The Author(s).)

Background: We investigated the impact of follow-up duration to determine whether two immunohistochemical prognostic panels, IHC4 and Mammostrat, provide information on the risk of early or late distant recurrence using the Edinburgh Breast Conservation Series and the Tamoxifen vs Exemestane Adjuvant Multinational (TEAM) trial., Methods: The multivariable fractional polynomial time (MFPT) algorithm was used to determine which variables had possible non-proportional effects. The performance of the scores was assessed at various lengths of follow-up and Cox regression modelling was performed over the intervals of 0-5 years and >5 years., Results: We observed a strong time dependence of both the IHC4 and Mammostrat scores, with their effects decreasing over time. In the first 5 years of follow-up only, the addition of both scores to clinical factors provided statistically significant information (P<0.05), with increases in R(2) between 5 and 6% and increases in D-statistic between 0.16 and 0.21., Conclusions: Our analyses confirm that the IHC4 and Mammostrat scores are strong prognostic factors for time to distant recurrence but this is restricted to the first 5 years after diagnosis. This provides evidence for their combined use to predict early recurrence events in order to select those patients who may/will benefit from adjuvant chemotherapy.

The guidelines for follow-up of breast cancer patients concentrate on the first 3-5 years, with either reduced frequency of visits or discharge after this. They also recommend mammography, but no evidence exists to inform frequency. We analyse treatable relapses in our unit from 1312 patients with early stage breast cancer treated by breast conserving surgery (BCS) and postoperative radiotherapy between 1991 and 1998 to assess appropriateness of the guidelines. A total of 110 treatable relapses were analysed. Treatable relapse developed at 1-1.5% per year throughout follow-up. Forty-eight relapses were in ipsilateral breast, 25 ipsilateral axilla, 35 contralateral breast, 2 both breasts simultaneously. Thirty-seven relapses (33.5%) were symptomatic, 56 (51%) mammographically detected, 15 (13.5%) clinically detected, 2 (2%) diagnosed incidentally. Mammography detected 5.37 relapses per 1000 mammograms. Patients with symptomatic or mammographically detected ipsilateral breast relapse had significantly longer survival from original diagnosis (P=0.0002) and from recurrence (P=0.0014) compared with clinically detected. Treatable relapse occurs at a constant rate for at least 10 years. Clinical examination detects a minority (13.5%). Relapse diagnosed clinically is associated with poorer outcome. Long-term follow-up based on regular mammography is warranted for all patients treated by BCS.

The CYP19 gene codes for the aromatase enzyme that is involved in the synthesis of oestrogens. This case-control study examines the relationship between a tetranucleotide repeat sequence in the CYP19 gene and the development of male breast cancer. No significant differences were found between male breast cancer cases and controls.

The CYP17 gene codes for the cytochrome P450c17alpha enzyme that is involved in the synthesis of oestrogens. This case-control study from the South East of Scotland shows that a polymorphism of the CYP17 gene is associated with an increased risk of male breast cancer.