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Cognitive Function, Fatigue and Menopausal Symptoms in Women Receiving Adjuvant Chemotherapy for Breast Cancer

Posted on: Friday, 22 October 2004, 03:00 CDT

Objective:

To determine whether cognitive function impairment, fatigue and menopausal symptoms contribute to the quality of life changes that occur in women receiving adjuvant chemotherapy for breast cancer.

Introduction:

The benefit on survival of adjuvant chemotherapy in women with breast cancer is well described in large randomized clinical trials and meta-analyzes. Short- and long-term side effects and changes in quality of life do occur1.

However, most women are prepared to tolerate adjuvant chemotherapy even for small survival gains2, and indeed in metastatic disease many women are prepared to trade quality of life for survival gains3.

Fatigue is a multifactorial symptom in all stages of cancer, with physical and psychological elements due to the disease itself, but also due to the treatment. Anaemia contributes to fatigue and is treatable and in some cases preventable. Menopausal symptoms are another short- and long-term side effect of chemotherapy (and endocrine therapy) in patients treated for breast cancer. Treatment options for these symptoms are limited and ineffective for a large percentage of women. Cognitive function has been shown to deteriorate more during chemotherapy for breast cancer than with surgery alone. How much this contributes to a woman's quality of life or indeed her functioning in everyday life at home and at work, is not known. Cognitive function and fatigue are now being linked and there is also a report of improvement in cognitive function on treatment with erythropoietin.

The authors of this article have done some exploratory work on cognitive function and this paper takes this further with examination of links to fatigue, menopausal symptoms and ultimately quality of life.

Methods:

Patients were < / = 60 years of age and spoke English. Patients nominated a control who could he either a relative or friend within 5 years of their own age. Menopausal status was documented on the hasis of menstrual history. Various chemotherapy regimens were included. Assessments were taken 2 - 6 weeks after > / = a third course of chemotherapy. Neuropsychologic tests for cognitive function included the HSCS (previously used hy this group), the mini- mcntal status exam, the trail-making test and the computer interactive test Conner's Continuous Performance Test (CPT). FACT - general, fatigue, and endocrine symptoms were used for the other symptoms. Blood was taken for hormone levels.

Based on previous studies, 100 pairs of patients and controls was considered feasible and with 4 end-points (HSCS, fatigue, menopausal symptoms and glohal evaluation), a p value of < 0.01 was regarded as significant for the two sided test. An exploratory multivariate analysis was also carried out to look at other factors contributing to cognitive function, fatigue, menopause and quality of life.

Results:

Patients and controls:

Of 291 eligible patients, 110 pairs of patients and controls were analyzed. They were well matched for age, menopausal status, parity and educational level. Only five were taking tamoxifen.

Individual symptoms:

* Moderate to severe global cognitive impairment was more common in patients 16% versus 4% (p = 0.008), but this was lower than expected from previous reports (17-50%). In particular looking at the six domains covered in the HSCS assessment there was a trend for language, attention, self-regulation and planning to be worse in patients than in controls, but no difference in memory or visual- motor performance. The CPT and trial-making test showed no difference between patients and controls.

* Using the FACT-F scale for fatigue patients had significantly more fatigue than controls with a score of 31 versus 46, p < 0.0001.

* Of the 62% of patients with regular menstruation before chemotherapy, only 25% were menstruating afterwards and this was confirmed by blood tests showing a menopausal state. Accordingly patients had significantly more menopausal symptoms (p < 0.001).

* From the FACT-G quality of life assessment, patients had inferior quality of life compared to controls in all domains (p < 0.0001), except the family-social subscale.

Inter-relationshp:

* No correlation between cognitive function and other symptoms or quality of life.

* Strong relationship between fatigue and quality of life p < 0.0001.

* Strong relationship between menopausal symptoms and quality of life p < 0.0001.

* Strong relationship between fatigue and menopausal symptoms p < 0.0001.

Exploratory multiviariate analysis:

* As the incidence of cognitive impairment was lower than predicted the model did not have the power to predict a relationship, but no trends were seen.

* Menopausal symptoms accounted for 30% of fatigue and fall in haemoglobin accounted for 5% of fatigue.

* No contributory factors to menopausal symptoms were found.

Conclusions:

This study confirms that quality of life during chemotherapy is impaired by fatigue and menopausal symptoms. The changes in cognitive function, while present, are not as frequent as previously suggested and do not appear to contribute to quality of life. This study group will be followed up at 1 and 2 years and this will be important data. Little was made of acute toxicities which must contribute to the on-treatment quality of life.

We are thus left with the situation of fatigue being our major challenge at this point in time. A small improvement can be hoped for with erythropoietin. The treatment of menopausal symptoms should be addressed more actively and prospectively, and the use of prophylactic approaches should be studied. On a positive note, women appear to cope with the cognitive functioning changes which is probably a reflection of their great coping skills!

Tchen N, Juffs HG, Downie FP, Qi-Long Y, Hanzian H, Chemcrynsky I, demons M, Crump M, Goss PE, Warr D, Tweedale ME, Tannock IF. J Clin Oncol 2003;21:4175-83

Selected references and further reading:

1. Hurny C, Bernhard J, Coates AS, Castiglione-Gertsch M, et al. Impact of adjuvant therapy on quality of life in women with node positive operable breast cancer. International Breast Cancer Group. Lancet 1996;347:1279-84

2. Lindley C, Vasa S, Sawyer WT, Winer EP. Quality of life and preferences for treatment following systemic adjuvant therapy for early stage breast cancer. J Clin Oncol 1998;16:1380-7

3. McLachlan SA, Pintilie M, Tannock IF. Third line chemotherapy in patients with metastatic breast cancer, an evaluation of quality of life and cost. Breast Cancer Res Treat 1999;54:213-23

Commentary by: Mary O'Brien, MD, MRCP, Kent Oncology Centre, Barming, UK

Copyright CRC Press Jun 2004

Source: Women's Oncology Review

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