Pain at 12 Months After Surgery for Breast Cancer

Persistent pain following breast cancer treatments remains a significant clinical problem despite improved treatment strategies.¹ Data on factors associated with persistent pain are needed to develop prevention and treatment strategies and to improve the quality of life for breast cancer patients. This prospective study examined the prevalence and severity of and the factors associated with chronic pain after breast cancer surgery and adjuvant treatments.

Consecutive patients younger than 75 years with unilateral nonmetastasized breast cancer treated at the Helsinki University Central Hospital in 2006-2010 with either breast-conserving surgery or mastectomy with axillary surgery were eligible. Patients receiving neoadjuvant treatment or immediate or delayed breast reconstruction or who had no breast cancer in the final histology were excluded. All women gave informed written consent. The ethics committee of the Helsinki University Central Hospital approved the study.

Preoperatively, medical history, demographic data, Beck Depression Inventory,² and Spielberger State-Trait Anxiety Inventory³ were obtained. Preoperative pain in the operative area (breast, axilla, arm) during the previous week was assessed with a numerical rating scale of 0 to 10 (0 = no pain; 1-3 = mild; 4-6 = moderate; ≥7 = severe).⁴ Perioperative analgesia was standardized. All patients received acetaminophen and patient-controlled analgesia with intravenous oxycodone. Postoperatively, data were acquired on tumor and lymph node characteristics, complications of surgery, reoperations, and the prognostic risk category.⁵ Adjuvant treatments were given according to international guidelines.⁵

A questionnaire was sent to patients 12 months after surgery, with identical assessments of presence and intensity of pain. A bivariable analysis was conducted to determine factors related to pain at 12 months after surgery. The worst pain in any area was used for statistical analysis, in which pain was considered an ordinal variable. Variables with P < .10 in bivariable analyses were entered into an ordinal logistic regression analysis. All statistical tests were 2-sided with P < .05 considered statistically significant. SPSS Statistics version 20 (SPSS Inc) software was used.

Of 1536 eligible women, 387 were not recruited due to logistic reasons (no research nurse available if operation started late), 126 declined, and 23 were excluded after recruitment (eg, because of change of type of operation). Thirty patients were later excluded because final histology indicated no cancer. Of the remaining 970 patients, 860 (88.7%) responded at 12 months to the questionnaire. Patient, tumor, and treatment characteristics appear in Table 1. The mean (SD) age of the patients was 57.3 (9.4) years; 24% had a chronic pain condition (eg, fibromyalgia, low back pain), the mean (SD) maximum pain intensity in the operative area was 1.3 (1.5), 73% received radiotherapy, and 57% received chemotherapy.

At 12 months after surgery, 34.5% (95% CI, 31.4%-37.8%) of the patients reported no pain, 49.7% (95% CI, 46.3%-53.0%) mild pain, 12.1% (95% CI, 10.0%-14.5%) moderate pain, and 3.7% (95% CI, 2.6%-5.3%) severe pain.

The factors significantly associated with pain at 12 months were chronic preoperative pain, preoperative pain in the area to be operated, preoperative trait anxiety, axillary lymph node dissection, chemotherapy, and radiotherapy (Table 2).

This prospective study found that 50% of patients had mild pain and 16% had moderate to severe pain 1 year after breast cancer surgery and identified factors associated with persistent pain. Chronic preoperative pain, axillary lymph node dissection, radiotherapy, and adjuvant chemotherapy have been associated with persistent pain in previous, mainly retrospective studies, which have been inconclusive regarding the effect of preoperative psychological factors.

These findings may be useful in developing strategies for preventing persistent pain following breast cancer treatment. To identify patients who would benefit from preventive interventions, a risk assessment tool is needed. We used the first half of the patients of the current cohort to develop a 6-factor model for pain at 6 months.⁶ However, the 6-factor model did not include any treatment-related factors.

A limitation of the study is that we did not perform a detailed clinical investigation at 1 year to diagnose the type of persistent pain.

Correction: This letter was corrected online on April 25, 2017, for incorrect data in the text and tables.

Corresponding Author: Tuomo J. Meretoja, Helsinki University Central Hospital, PO Box 140, FI-00029 HUS, Finland (tuomo.meretoja@fimnet.fi).

Author Contributions: Dr Meretoja had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Leidenius, Tasmuth, Kalso.

Acquisition of data: Leidenius, Tasmuth, Kalso.

Analysis and interpretation of data: Meretoja, Leidenius, Tasmuth, Sipilä, Kalso.

Drafting of the manuscript: Meretoja, Leidenius, Kalso.

Critical revision of the manuscript for important intellectual content: Meretoja, Leidenius, Tasmuth, Sipilä, Kalso.

Statistical analysis: Meretoja.

Obtained funding: Meretoja, Kalso.

Administrative, technical, or material support: Tasmuth, Kalso.

Study supervision: Kalso.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Kalso reported serving as a consultant to Pharmaleads and Orion Pharma; receiving payment for lectures from Pfizer, Mundipharma, Jansen-Cilag, Merck Sharp Dohme, Gruenental, and Orion Pharma; holding patents with Orion Pharma and Licentia (formerly the University of Helsinki patent office); receiving payment for the development of educational presentations from Jansen-Cilag and Gruenenthal; and owning stock in Orion Pharma.

Funding/Support: This work was supported by grants from the Academy of Finland and Helsinki and Uusimaa Hospital District and by funding from the Orion-Pharmos Research Foundation and the Emil Aaltonen Foundation.

Role of the Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We also thank Eija R. Ruoppa, RN, and Minna Kaiponen, RN (Department of Anaesthesia, Intensive care Medicine, Emergency Medicine and Pain Medicine, Helsinki University Central Hospital), and the nurses, physicians, and physiotherapists who participated in the treatment and recruitment of the patients. We are grateful to the patients who participated in this study and diligently returned several questionnaires. The persons named were not compensated for study assistance beyond their salaries.