Hormone replacement therapy in cancer survivors.

OBJECTIVE: Thousands of women are treated each year for cancer; many of these are already in menopause, while other younger patients will go into early menopause due to surgery, or chemotherapy, or the need for radiotherapy to the pelvic region. In most cases the oncologist and the gynaecologist would advise these women against the use of HRT. The purpose of this paper is to review biological and clinical evidences in favour and against HRT use in the different tumours and to propose an algorithm that can help choosing the treatment for the single woman. METHODS: We performed a systematic literature review through April 2002 concerning: (1) biological basis of hormonal modulation of tumour growth; (2) epidemiological data on the impact of HRT on different cancers risk in healthy women; (3) safety of HRT use in cancer survivors; (4) alternatives to HRT. RESULTS: With the exception of meningioma, breast and endometrial cancer, there is no biological evidence that HRT may increase recurrence risk. In women with previous breast and endometrial cancer HRT is potentially hazardous on a biological basis, even if published data do not show any worsening of prognosis. CONCLUSIONS: Even if a cautious approach to hormonal-dependent neoplasias is fully comprehensible and the available alternative treatment should be taken into greater consideration, the reticence to prescribe HRT in women previously treated for other non hormone-related tumours has neither a biological nor a clinical basis. An algorithm based on present knowledge is proposed.

Menopause after breast cancer: a survey on breast cancer survivors.

UNLABELLED: Due to the younger age and the ever wider use of adjuvant chemotherapy and antiestrogens, menopausal symptoms are a frequent cause of concern for breast cancer patients. OBJECTIVES: To determine the prevalence of menopausal symptoms, and to explore the attitudes toward Hormone Replacement Therapy (HRT) or other treatments and the willingness to take oestrogen in breast cancer patients. METHODS: A questionnaire-based survey on 250 breast cancer patients treated and followed-up at our department. Of them 144 (Group A) were in postmenopause and 106 (Group B) were in premenopause at time of diagnosis. RESULTS: Adjuvant therapy with tamoxifen or tamoxifen plus chemotherapy is associated with a significant worsening of menopause-related symptoms of women belonging to Group A. These women are more concerned about risk of breast cancer recurrence than about risk of osteoporosis (P=0.05) and heart disease (P=0.006). Seventy-eight percent are against the use of HRT; only 22% would consider taking HRT mainly for vasomotor symptoms relief and osteoporosis prevention. The incidence of vasomotor and dystrophic symptoms is significantly higher in women belonging to Group B treated with chemotherapy and/or hormonotherapy as compared with postmenopausal women (P<0.000 and P=0.02, respectively). Premenopausal women are more concerned about risk of breast cancer recurrence than older women (P=0.09) and at the same time are significantly more worried about the impairment of the quality of life due to adjuvant therapy (P=0.005). Younger women are more prone to consider HRT than postmenopausal women (P=0.05). Sixty-six percent are against HRT use, and 34% would consider taking HRT to alleviate vasomotor and dystrophic symptoms and to prevent osteoporosis. CONCLUSIONS: Breast cancer survivors are interested to treatments that may improve their quality of life, but fear of HRT persists among these women and their doctors, despite new evidence suggesting the low probability of detrimental effects.

The prognostic value of the human kallikrein gene 9 (KLK9) in breast cancer.

BACKGROUND: Many members of the human kallikrein gene family were found to be differentially expressed in various malignancies and some of them are useful diagnostic/prognostic markers. KLK9 is a newly discovered human kallikrein gene that is expressed in several tissues including thymus, spinal cord, testis, prostate, breast, and ovary. Like other kallikreins, the KLK9 gene was found to be regulated by steroid hormones, mainly estrogens and progestins, in cancer cell lines. EXPERIMENTAL DESIGN: We studied the expression of KLK9 by quantitative RT-PCR in 169 breast cancer patients of different stages, grades and histological types. We also compared the relation between KLK9 expression and other clinicopathological variables and patient survival. RESULTS: KLK9 expression is significantly higher in patients with early stage cancers (p = 0.039) and in patients with small tumor size (< 2 cm) (p = 0.028). Kaplan-Meier survival curves demonstrated that KLK9-positive patients have longer disease-free and overall survival (p = 0.015 and 0.036, respectively). Univariate and multivariate analysis also indicates that KLK9 expression is associated with increased disease-free and overall survival. When the Cox proportional hazard regression analysis was applied to subgroups of patients, KLK9 expression was found to be a significant predictor of disease-free survival in the estrogen receptor (ER) and progesterone receptor (PR) negative subgroups of patients (Hazard Ratio 'HR' = 0.28, and 0.38, respectively, and p = 0.011 and 0.028, respectively). After adjusting for other known prognostic variables, KLK9 retained its independent prognostic value in these subgroups of patients. Similar results were obtained for overall survival. CONCLUSIONS: KLK9 is a new potential independent marker of favorable prognosis in breast cancer.

Human kallikrein gene 5 (KLK5) expression by quantitative PCR: an independent indicator of poor prognosis in breast cancer.

BACKGROUND: KLK5 is a newly discovered human kallikrein gene. Many kallikrein genes have been found to be differentially expressed in various malignancies, and prostate-specific antigen (PSA; encoded by the KLK3 gene) is the best tumor marker for prostate cancer. Like the genes that encode PSA and other kallikreins, the KLK5 gene was found to be regulated by steroid hormones in the BT-474 breast cancer cell line. METHODS: We studied KLK5 expression in 179 patients with different stages and grades of epithelial breast carcinoma by quantitative reverse transcription-PCR (RT-PCR), using LightCycler((R)) technology. An optimal cutoff point equal to the detection limit (65th percentile) was used. KLK5 values were then compared with other established prognostic factors in terms of disease-free (DFS) and overall survival (OS). RESULTS: High KLK5 expression was found more frequently in pre-/perimenopausal (P = 0.026), node-positive (P = 0.029), and estrogen receptor-negative (P = 0.038) patients. In univariate analysis, KLK5 overexpression was a significant predictor of reduced DFS (P <0.001) and OS (P <0.001). Cox multivariate analysis indicated that KLK5 was an independent prognostic factor for DFS and OS. KLK5 remained an independent prognostic variable in the subgroups of patients with large tumors (>2 cm) and positive nodes. Hazard ratios derived from Cox analysis and related to DFS and OS were 2.48 (P = 0.005) and 2.37 (P = 0.009), respectively, for the node-positive group and 3.03 (P = 0.002) and 2.94 (P = 0.002), respectively, for patients with tumor sizes >2 cm. KLK5 expression was also associated with statistically significantly shorter DFS (P = 0.006) and OS (P = 0.004) in the subgroup of patients with grade I and II tumors. CONCLUSIONS: KLK5 expression as assessed by quantitative RT-PCR is an independent and unfavorable prognostic marker for breast carcinoma.