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In this issue of the Dutch Journal of Medicine (NTvG), Saadatmand and colleagues report the results of a large retrospective study on breast cancer patients in the Netherlands. One of their conclusions is that breast-conserving therapy results in better survival compared to breast amputation. Here we argue that retrospective studies are not designed to draw any conclusions with regard to outcome. Confounding by indication is the main reason why differences in outcome may not be causally connected in the context of retrospective data. In the case of different options for breast cancer surgery, many randomised trials have firmly concluded that survival is not influenced by type of surgery. Despite the association found in this retrospective analysis, this study does not alter that conclusion.

Old age is strongly associated with comorbidity and decreased functioning, which in turn affects treatment decisions for elderly breast cancer patients. In recent years, the rate of elderly patients with breast cancer who were not operated on has increased considerably. Older age and an increased number of concomitant diseases are associated with an increased risk of postoperative complications. Mortality is higher in patients who experience complications than in patients who do not. The death of a patient who experiences a complication does not result from the complication itself; rather, it is associated with factors that make such a patient vulnerable e.g. comorbidity and poor functional status. Hormonal therapy could be a good alternative for surgical treatment in vulnerable elderly patients, but sound research into this is lacking. Deciding against the surgical treatment of elderly patients with breast cancer based on the fear of postoperative mortality is not justifiable; however, there is too little evidence on the consequences of breast cancer surgery on outcome measures such as quality of life and functional status yet available to be able to offer strong recommendations on the surgical treatment of elderly patients with breast cancer.

Objective: To evaluate the long-term results of 20 years of experience with isolated limb perfusion (ILP) with tumour necrosis factor α (TNF-α) and melphalan, followed by surgical resection and adjuvant radiotherapy, for the treatment of advanced soft tissue sarcomas of the extremities., Design: Retrospective cohort study., Method: From 1991 to 2011, 113 patients with primary irresectable soft tissue sarcomas underwent 117 ILPs at the University Medical Centre Groningen. 96 ILPs (82%) were performed in the lower limb, and 21 (18%) in the upper limb. The dosages used were 1-4 mg TNF-α and 10-13 mg/l melphalan., Results: After a median follow up of 8 (range 2-15) weeks after ILP, 107 tumours were resected: 81 (76%) of the resection margins were tumor-free. After the resection, 69 patients (61%) received adjuvant radiotherapy. In total, 85 ILPs resulted in a tumoural response; 16 patients (14%) developed a local recurrence and after 46 treatments (39%), distant metastases had developed. After a median follow-up of 51 months, the limb had been spared in 88 patients (78%). The 10- year disease-specific survival was 53.8%. There was a median follow-up period of 76 months (range: 7-234); still alive at the end of this period were 56 patients (50%). A total of 83 perfusion- or resection-related complications occurred from 58 ILPs (50%): 55 (66%) early and 28 (34%) late treatment-related complications. None of the patients died as a result of the treatment., Conclusion: ILP is a safe and effective procedure in the treatment of advanced primary irresectable soft tissue sarcoma that can prevent amputation in many cases. It is however associated with significant morbidity and is burdensome for the patient.

The prognosis for older post-menopausal breast cancer patients is worse than for younger post-menopausal patients. This applies to the relatively healthy patients taking part in randomized clinical studies, but is also the case for older breast cancer patients in the general population. The worse prognosis may be explained by inadequate treatment, and possibly also by age-specific tumour and patient characteristics. As older patients are rarely included in randomized trials, it is still insufficiently clear what constitutes adequate treatment for them. It is therefore important to include more elderly patients in clinical studies into the effectiveness of breast cancer therapy. An important aim is to allow correct assessment of which patients will die with, and which patients will die from breast cancer, so that treatment can be adjusted accordingly.

Despite the high prevalence of breast cancer in the elderly population, these individuals are underrepresented in clinical trials evaluating breast cancer. Extrapolation from a young trial group to the heterogeneous elderly population is not justified; the elderly more often present with well-differentiated tumours and positive hormone-receptor status. Moreover, increasing age is associated with changes in organ functioning which may interfere with treatment efficacy and toxicity. Finally, the impact of breast cancer on the expected longevity of such patients decreases with age. Therefore, the treatment of elderly breast cancer patients, as recommended by national guidelines, is not evidence-based. Because of the great heterogeneity, randomized trials are difficult to achieve in the elderly. We therefore stress the importance of alternative study designs to realise evidence-based medicine in this ever-growing population.