Alan W. Lees

The Addition of Manual Lymph Drainage to Compression Therapy For Breast Cancer Related Lymphedema: a Randomized Controlled Trial

AbstractPurpose. The purpose of this investigation was to compare the reduction in arm lymphedema volume achieved from manual lymph drainage massage (MLD) in combination with multi-layered compression bandaging (CB) to that achieved by CB alone. Methods and materials. Fifty women with lymphedema (mean age of 59 years ± 13 years) were randomly assigned to 4 weeks of combined MLD/CB or CB alone. The primary study endpoint was the reduction in arm lymphedema volume, which was determined by water displacement volumetry and measurement of circumference. Independent assessors, blinded to subject treatment assignment, performed the outcome measurements. Results. Arm lymphedema volume decreased significantly after 4 weeks irrespective of treatment assignment (p < 0.001). Individuals with mild lymphedema receiving combined MLD/CB had a significantly larger percentage reduction in volume compared to individuals with mild lymphedema receiving CB alone, and compared to individuals with moderate or severe lymphedema receiving either treatment. Conclusion. These findings indicate that CB, with or without MLD, is an effective intervention in reducing arm lymphedema volume. The findings suggest that CB on its own should be considered as a primary treatment option in reducing arm lymphedema volume. There may be an additional benefit from the application of MLD for women with mild lymphedema; however, this finding will need to be further examined in the research setting.

Risk factors and 10-year breast cancer survival in Northern Alberta

Summary1,121 women in northern Alberta diagnosed as having breast cancer between 1971–74 were followed for 10 years. Risk factors for breast cancer were studied with respect to their possiblé influence on survival by comparing survival curves, using both Logrank and Coxs regression model, and controlling for intercurrent death, stage and axillary node status.A complex interaction was found between age and menopausal status and survival rates. Premenopausal women aged 45–55 had a better survival rate than postmenopausal women of the same age. However, one subgroup of premenopausal women aged 35–39 had a significantly worse prognosis than those aged 40–44 as did a group of post menopausal women aged 70–74. No cause was found other than the effect of age.There was a significant trend to worsening survival with heavier weight at time of diagnosis and with breast feeding. Parity of five or more and family history of breast cancer were less consistently associated with worse survival. Oral contraceptive use was only associated with worsened prognosis significantly when stage was controlled for; there was no overall effect. Age at menarche and age at first birth did not influence prognosis. Theories to explain the findings are discussed.

Brain metastases in breast cancer patients receiving adjuvant chemotherapy

A retrospective analysis was performed comparing the incidence of brain metastases as a site of first recurrence in patients receiving adjuvant chemotherapy during the period from 1973–1979 for node‐positive operable carcinoma of the breast, compared to a matched control group of patients presenting during the same period treated by local measures only. Five of 115 patients (4.3%) receiving adjuvant chemotherapy have had brain metastases as first site of distant recurrence compared to zero of 115 (0%) in the control group. This comprised 12.8% of first distant recurrences in the adjuvant group. The authors suggest that this increased incidence of brain metastases, as site of first recurrence, reflects prolonged suppression of systemic disease by adjuvant chemotherapy with less effect in controlling metastases in the brain.

Mood Disorder in Women with Early Breast Cancer Taking Tamoxifen, an Estradiol Receptor Antagonist

Breast cancer is the commonest malignancy in women and the most important cause of death in women age 34 to 54. Tamoxifen, an estradiol receptor antagonist, prevents or delays growth of estrogen-dependent breast tumors. The drug, initially used in advanced disease in postmenopausal women, is now used as adjuvant therapy in preand postmenopausal women; preventive trials are underway in women at high breast cancer risk. Pharmacological and clinical evidence suggests that steroid hormones may influence mood. Problems occur with birth control pills (depression), anabolic steroids (euphoria, aggression, ‘droid rage,’ addiction), glucocorticoids (psychological dependence, euphoria, mood swings, depression), gestagens (nervousness, depression), and estrogenic drugs (irritability, nervousness, depression). Estrogen withdrawal (premenstrual syndrome, postpartum, and at menopause) may be associated with various dysphoric symptoms. Tamoxifen appears to induce mood problems in only a small percentage of patients (fewer than 1 %).I Clinical impression suggested that more women may be affected than is estimated and that the drug’s impact on mood and quality of life required exploration.

The treatment of carcinoma of the anterior two-thirds of the tongue by radiotherapy

Abstract Results are presented of the retrospective analysis of the treatment of 139 patients having carcinoma of the anterior two-thirds of the tongue in the Leeds Region from 1962 to 1972. The disease is much less common in men than has been reported in the past and the prognosis in men in this series is better than in women. Overall survival, age corrected, is 42% at 5 years for men, 33% for women. Patients were followed for a minimum of 2 years. The majority of patients were treated by radiotherapy using implants, implants and external beam therapy, and external beam therapy alone. The efficacy of these methods for controlling the primary tumor is assessed by examining results at 1 year after treatment, since the majority of treatment faffures occurred before this time. By relating these control rates to the dose given, dose response curves were constructed which suggest that the relationship between dose and response is not as steep for carcinoma of the anterior two-thirds of the tongue as for supraglottic laryngeal cancer. For T 2 and T 3 tumors, the therapeutic ratio shows little or no increase with dose. Evidence for an optimum dose for each size of tumor is discussed. A large number of patients with tongue cancer die from uncontrolled cancer in the regional nodes but with the primary tumor controlled. The optimum management of regional lymph nodes is not resolved, although in this series, surgical resection of the nodes gives better results than radiotherapy.

Response to treatment and its influence on survival in metastatic breast cancer

THE CLINICAL RESPONSE TO FIRST SYSTEMIC THERAPY of 381 patients with metastatic breast cancer was assessed; the influence of the category of this first response on eventual survival from diagnosis of first distant metastasis was analyzed. Survival from diagnosis of first distant metastasis was found to be similar whether the patient had a complete response, a partial response, or stable disease; only when progressive disease occurred with first systemic treatment was survival significantly shortened. This similarity in survival whatever the category of response from diagnosis of first distant metastases was found whether the patient received chemotherapy or hormone therapy as first systemic treatment, and whether the patient was premenopausal or post-menopausal; there was some suggestion on analysis of premenopausal patients treated with hormone therapy as first systemic therapy that a complete response conferred a survival advantage, but the numbers were small in this group. When complete re-sponders to first systemic therapy as well as any other subsequent systemic therapy were analyzed for survival from diagnosis of first distant metastasis, again, no survival advantage could be found compared to the other response categories, but the complete response rate was low owing to the unselected nature of this group of study patients.It is concluded that the categories of complete, partial, or stable response to therapy have no great significance in terms of survival; the category of progressive disease to first systemic therapy is, however, associated with a shorter survival in all the analyses performed. We suggest that assessment of a treatments worth should be based as much on the patients subjective feeling of well-being as on the magnitude of the tumor response, since with currently available therapies, provided some form of response is obtained, the magnitude of the response does not appear to translate into any major survival advantage. This study points up the disparity between research-oriented criteria of response (survival, response rate, and its magnitude) and patient care criteria of response (survival and quality of life).

Three-Arm Randomized Phase III Trial: Quality Aloe and Placebo Cream Versus Powder as Skin Treatment During Breast Cancer Radiation Therapy

BACKGROUND The efficacy of aloe extract in reducing radiation-induced skin injury is controversial. The purpose of the present 3-arm randomized trial was to test the efficacy of quality-tested aloe extract in reducing the severity of radiation-induced skin injury and, secondarily, to examine the effect of a moist cream versus a dry powder skin care regimen. MATERIALS AND METHODS A total of 248 patients with breast cancer were randomized to powder, aloe cream, or placebo cream. Acute skin toxicity was scored weekly and after treatment at weeks 1, 2, and 4 using a modified 10-point Catterall scale. The patients scored their symptom severity using a 6-point Likert scale and kept an acute phase diary. RESULTS The aloe formulation did not reduce acute skin toxicity or symptom severity. Patients with a greater body mass index were more likely to develop acute skin toxicity. A similar pattern of increased skin reaction toxicity occurred with both study creams compared with the dry powder regimen. CONCLUSION No evidence was found to support prophylactic application of quality aloe extract or cream to improve the symptoms or reduce the skin reaction severity. Our results support a dry skin care regimen of powder during radiation therapy.

Tamoxifen in Breast Cancer: Symptom Reporting

Abstract: Clinical studies have traditionally identified treatment‐specific side effects by comparison of voiced side effects in treatment and placebo arms of a study. Highly motivated women in a clinical trial may underreport drug‐induced symptoms for medications which may be considered lifesaving. Affective symptoms during treatment of early breast cancer with tamoxifen (an estradiol receptor antagonist) were reported as infrequent by the manufacturer. However, reports suggest a higher rate of depression during general use. The objective of the present study was to examine the frequency of symptoms that might be side effects of tamoxifen and to relate them to the way the women attributed such symptoms. The exploratory study involved semistructured telephone interviews of 25 women who were taking tamoxifen. Textual analysis of the information was used to examine the symptoms described by the women. They were also asked whether any symptoms were related to the medication. The symptoms and their attribution were evaluated against a background of self‐perceived stress. The principal finding was a pattern of ambivalence in attributing symptoms to the drug. Of all the symptomatic changes noted, the women only attributed 51% to tamoxifen. Flushes, fatigue, and depression were reported most frequently during treatment; flushes were readily attributed to tamoxifen but depression and fatigue were attributed to another factor by half of the symptomatic women. Women who reported moderate to high levels of life stress were less likely to attribute symptoms to drug therapy. The results suggest that women taking tamoxifen may not attribute known drug side effects to use of the medication.

Interactions between benign breast disease and other risk factors for breast cancer

A population-based incident case-control study of breast cancer in Northern Alberta, Canada, provided an opportunity to evaluate interactions between the occurrence of benign breast disease (BBD) and other potential risk factors. Overall there was a 2-fold excess risk of breast cancer among women with BBD. This excess persisted regardless of the number of years from first biopsy for BBD to diagnosis of breast cancer, suggesting a permanent alternation in risk with BBD. Significant variations of the BBD--breast cancer association were noted with several factors. The excess risk of breast cancer among women with BBD was enhanced by having a later age at menarche, a later age at first birth, or lower parity. The usual protective effect of late age at menarche was seen only among women without BBD, and was supplanted by a 4-fold elevated risk among women with BBD. The deleterious effects of later age at first birth and nulliparity were greater among women with BBD. These patterns generally support the notion that hormonal factors mediate the relation between BBD and the development of breast cancer.

Trends in the incidence of cancer of the female breast and reproductive tract in Alberta, 1953 to 1977.

A log-linear model was used to separate age, secular, and cohort trends in the incidence of cancer of the breast, ovary, corpus uteri, cervix uteri, vagina, and vulva in female residents in Alberta over the period 1953 to 1977. The age trends are similar for each cancer site increasing sharply in the premenopausal period and then leveling off. In the case of breast cancer, a point of inflection at the menopause (Clemmesens hook) persists. A gradually increasing secular trend in incidence was evident for all sites except cervix uteri, the incidence of which declined after 1960. Cyclical cohort trends were found for cancers of the breast, ovary, and corpus uteri, inversely correlated with early fertility. The cohort trends for cervix uteri, vagina, and vulva increased sharply for cohorts born after 1940.