Randomized clinical trials

Coles CE, Haviland JS, Kirby AM, Griffin CL, Sydenham MA, Titley JC et al, on behalf of the IMPORT Trial Management Group.

Lancet 2023; 401: 2124-2137.

A total of 2617 women were enrolled in the trial. Concomitant booster irradiation was safe, with similar rates of local recurrence: 2 per cent and 3.2 per cent in the different dosages, compared to 1.9 per cent in controls. Simultaneous booster irradiation reduced patient visits.

Comment: Easier for the women, and should improve treatment scheduling.

Piatkowski AA, Wederfoort JLM, Hommes JE, Schop SSJ, Krastev TK, van Kuijk SMJ et al, for the Breast Reconstruction With External Preexpansion & Autologous Fat Transfer vs Standard Therapy (BREAST) Trial Investigators.

JAMA Surg 2023; 158: 456-464.

There was no evidence that fat transfer was unsafe in this study that included 193 women. Quality of life was improved in all five domains in women who had the fat transfer procedure in the 132 women who completed the study (all domains P<0.05). There were no differences in complications or oncological outcomes.

Comment: Less invasive than breast reconstruction.

Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).

Lancet 2023; 491: 1277-1292.

This huge analysis of women treated for breast cancer showed that the combination of anthracycline and taxane regimens was most effective at reducing breast cancer recurrence. The higher dose regimens produced the greatest effects.

Comment: I really admire this sort of analysis which provides very important information that influences treatment strategies.

Kunkler IH, Williams LJ, Jack WJL, Cameron DA, Dixon JM.

N Engl J Med 2023; 388: 585-594.

The study included 1326 women aged 65 or over with ER+ve breast cancer completely excised. After a median follow-up of 9.1 years, the addition of whole breast radiotherapy reduced the risk of local recurrence (0.9 versus 9.5 per cent, P<0.0001), but did not affect overall survival: 80.7 versus 80.8 per cent, respectively.

Comment: Very helpful study that enables women to make a choice.

Zhang L, Cheng M, Lin Y, Zhang J, Shen B, Chen Y et al.

Br J Surg 2022; 109: 1232–1238.

In this study that included 330 women, the sentinel node identification rate was similar: 94.5 per cent with ultrasound assistance versus 95.8 per cent with dual tracer. Number of sentinel nodes, number of metastatic nodes and duration of surgery were similar between the groups.

Comment: Ultrasound-assisted carbon nanoparticle mapping was non inferior.

Stallard S, Savioli F, McConnachie A, Norrie J, Dudman K, Morrow ES et al.

Br J Surg 2022; 109: 1224–1231.

In this study that included 871 procedures, a single dose of Amoxicillin-clavulanic acid did not reduce the risk of wound infection up to 30 days: 16.2 per cent versus 19.2 per cent in controls, P=0.25.

Comment: not beneficial even in higher risk subgroups – obese or Staph aureus carriers.

Ben-Arye E, Hausner D, Samuels N, Gamus D, Lavie O, Tadmor T et al.

Cancer 2022; 128: 3641-3652.

In this study that included 168 patients, acupuncture, with or without other complementary therapies improved the symptoms of neuropathy, particularly hand numbness and discomfort (P=0.007) after six weeks, and improved emotional wellbeing (P=0.04).

Comment: Neuropathy is one of the most unpleasant side effects of chemotherapy, so this study gives optimism that it may at least be minimised by intervention.

Massimimiliano G, Maccauro M, Mariani L, Listorti C, Sigari C, De Vivo A et al.

Cancer 2022; 128: 4185-4193.

Reverse axillary mapping with selective axillary dissection reduced the rate of lymphoedema by 21 per cent (confidence intervals 3-37 per cent, P=0.03) in this study that included 130 patients. Self-reported rates of lymphoedema were not different between the groups.

Comment; Disappointing that the women did not notice a difference.

Stachs A, Bollmann J, Martin A, Stubert J, Reimer T, Gerber B et al.

BJS Open 2022; 6: zrac091.

The new radiology technique did not reduce the risk of positive resection margins (31.7 versus 26.3 per cent, P=0.127) in this study that included 122 procedures.

Comment: No benefit.

Chua BH, Link EK, Kunkler IH, Whelan TJ, Westenberg AH, Gruber G et al, on behalf of the BIG 3–07/TROG 07.01 trial investigators.

Lancet 2022; 400: 431-440.

This multicentre study included 1608 patients in a two by two design. The five-year freedom from recurrence rate was higher after booster radiotherapy (97.1 versus 92.7 per cent, P<0.001), but with higher rates of breast pain and induration.

Comment: Booster radiotherapy improved local control, and women can be warned concerning the after effects.

Toesca A, Sangalli C, Maisonneuve P, Massari G, Girardi A, Baker L, et al.

Ann Surg 2022; 276: 11-19.

Eighty women were included in this study. Robotic surgery took one hour and 18 minutes longer, but was associated with improved postoperative satisfaction, physical and sexual well-being. Complication rates were similar.

Comment: A cost effectiveness analysis is needed here.

Goodwin PJ, Chen BE, Gelmon KA, Whelan TJ, Ennis M, Lemieux J et al.

JAMA 2022; 327: 1963-1973.

This study included 3643 non diabetic women, who were followed for a median of 96.2 months. Metformin did not have any advantage for women with ER positive (hazard ratio for invasive disease-free survival 1.01, 95 per cent confidence interval 0.84 to 1.21, P=0.93) or ER negative breast cancer (1.01, 0.79 to 1.3, P=0.92).

Comment: Science is the destruction of a beautiful idea by an ugly fact.

Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).

Lancet Oncol 2022; 23: 382-392.

Aromatase inhibitors were compared with tamoxifen in premenopausal women with ovarian suppression in a study that included 7030 patients followed for a median of eight years. Aromatase inhibitors reduce recurrence, especially in years 1 to 4 (13.2 per cent absolute risk reduction). Recurrence rates were similar in years 5 to 9. Mortality rates were also similar.

Comment: Initial treatment with aromatase inhibitors in this group seems optimal.

Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kummel S et al, for the KEYNOTE-522 Investigators.
N Engl J Med 2022; 386: 556-567.

Use of neoadjuvant pembrolizumab plus chemotherapy, with additional pembrolizumab postoperatively improved event-free survival from 76.8 to 84.5 per cent at 36 months in this study that included 1174 women.

Comment: New standard of care?

Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF et al.
N Engl J Med 2021; 385: 2336-2347

The study included 5083 women with hormone receptor positive, HER 2 negative breast cancer with 1-3 positive axillary nodes and a recurrence score above 25. They all received endocrine therapy, and were randomized to additional chemotherapy. Five year overall survival rates were not improved with chemotherapy: 91.3 versus 91.9 percent, but disease-free survival was better in premenopausal women.

Comment: A large and complex trial that helps inform how to mange women with node positive breast cancer.