Survival from breast cancer in relation to access to tertiary healthcare, body mass index, tumor characteristics and treatment: a Hellenic Cooperative Oncology Group (HeCOG) study

Abstract

Apart from tumour, treatment and patient characteristics at diagnosis, access to healthcare delivery may as well play a significant role in breast cancer prognosis. This study aimed to assess the additional impact exerted on survival by travel burden—a surrogate indicator of limited access to healthcare- expressed as geographical distance and/or time needed to reach the tertiary healthcare center from the patient’s residence. Between 1997 and 2005, 2,789 women participated in therapeutic clinical trials conducted by the Hellenic Cooperative Oncology Group. The effect of geographical distance and travel time between patient’s residence and treating hospital on survival was estimated using Cox proportional hazards regression adjusting for age, menopausal status, tumour size/grade, positive nodes (number), hormonal receptor status, HER2 overexpression, surgery type/treatment protocol as well as for body mass index >30 kg/m². More aggressive tumour features, older treatment protocols and modifiable patient characteristics, such as obesity (HR: 1.27) adversely impacted on breast cancer survival. In addition, less studied indicators of access to healthcare, such as geographic distance >350 km and travel time >4 h were independently and significantly associated with worse outcomes (HR = 1.43 and 1.34 respectively). In conclusion, to address inequalities in breast cancer survival, improvements in access to healthcare services related to increased travel burden especially for patients of lower socioeconomic status should be considered, more than ever at times of financial crisis and independently of already known modifiable patient characteristics.

Appendix: Clinical studies

• 1. HE 10/97 trial was a randomized phase III trial in patients with high-risk node-negative or node-positive operable breast cancer, comparing four cycles of epirubicin followed by four cycles of CMF (E-CMF) with three cycles of epirubicin, followed by three cycles of paclitaxel followed by three cycles of CMF (E-T-CMF). All cycles were given every two weeks with granulocyte-colony stimulating factor (G-CSF) support. Dose intensity of all drugs in both treatment arms were identical, but cumulative doses and duration of chemotherapy period differed. Totally, 595 eligible patients entered the study in a period of 3.5 years (1997–2000).

• 2. HE 10/00 was a randomized phase III trial in which a total of 1086 eligible patients with node-positive operable breast cancer were accrued in a period of 5 years (2000–2005). Patients were treated with E-T-CMF (exactly in the HE 10/97 trial) or with four cycles of epirubicin/paclitaxel combination every three weeks followed by three cycles of CMF every two weeks (ET-CMF). By study design, the cumulative doses and the duration of chemotherapy period were identical in the two arms but dose–intensity of epirubicin and paclitaxel was double in the E-T-CMF arm. Treatment schedules in the two studies are described in detail in Table S1 (Supplementary only). Baseline characteristics and clinical outcomes have been published.

• 3. HE 10/04 were two consecutively conducted feasibility studies in which 44 and 45 eligible patients with node-positive or high-risk node-negative breast cancer were accrued in 2004. Patients were treated with three cycles of epirubicin followed by three cycles of CMF (at the same dosage as in the HE 10/97 trial) followed by nine weekly cycles of paclitaxel or nine weekly cycles of docetaxel respectively.

• 4. HE 10/05 was a randomized phase III trial in which a total 1001 eligible patients with node-positive or high-risk node-negative operable breast cancer were accrued in a period of 3 years (2005–2008). Patients were treated with E-T-CMF (as in the 10/97 trial but with a lower dose of paclitaxel, 200 mg/m²) or 3 cycles of epirubicin followed by 3 cycles of intensified CMF followed by 8 cycles of weekly paclitaxel or docetaxel (as in HE 10/04 trial) (unpublished data). All studies were designed and conducted by the Hellenic Cooperative Oncology Group (HeCOG).

All clinical protocols were approved by local regulatory authorities. Additionally, the randomized trials HE 10/97, HE 10/00 and HE 10/05 were included in the Australian New Zealand Clinical Trials Registry (ANZCTR) and allocated the following Registration Numbers: ACTRN12611000506998, ACTRN12609001036202 and ACTRN12610000151033, respectively. Each patient signed a study-specific written informed consent before randomization which in addition allowed the use of biological material for future research purposes.