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N Biglia

Publications and source records attributed to N Biglia.

At least 19 recordsLinked to original sources
PubMed2006

Clinical outcome of adjuvant endocrine treatment according to PR and HER-2 status in early breast cancer.

Patients with estrogen receptor (ER)+/progesterone receptor (PR)- and/or HER-2 overexpressing breast carcinomas may derive lower benefit from endocrine treatment. We examined retrospectively data from 972 breast cancer patients who received tamoxifen (725), tamoxifen + Gn-RH analogs (127) and aromatase inhibitors (120) as adjuvant treatments. ER+/PR- versus ER+/PR+ tumours were characterised by larger size (P = 0.001), higher tumour grade (P = 0.001), higher Ki-67 expression (P = 0.001) and lower mean ER (P = 0.000) and HER-2 expression (P = 0.000). At univariate analysis, tumour grading [hazard ratio (HR) = 4.0; 95% confidence interval (CI) = 1.4-11.1; P = 0.007], nodal status (HR = 3.4; 95% CI 1.2-5.7; P = 0.000), tumour diameter (HR = 2.9; 95% CI 1.7-4.7; P = 0.000) lack of PR expression (HR = 2.1; 95% CI 1.3-3.4; P = 0.002) and HER-2 overexpression (HR = 1.9; 95% CI 1.0-3.5; P = 0.03), as well as Ki 67 expression (HR = 1.7; 95% CI 1.0-2.7; P = 0.04) were associated with shorter disease-free survival (DFS). At the multivariate analysis, nodal status (HR = 3.6; 95% CI 1.9-6.8; P = 0.0001), lack of PR expression (HR = 2.3; 95% CI 1.3-4.0; P = 0.003) and tumour diameter (HR = 2.1; 95% CI 1.1-3.8; P = 0.018) retained their prognostic significance, whereas HER-2 overexpression was associated with a trend towards shorter DFS that was of borderline statistical significance (HR = 2.0; 95 % CI 1.0-3.9; P = 0.05). Our data suggest that lack of PR expression and HER-2 overexpression are both associated with aggressive tumour features, but the prognostic information of PR status on the risk of recurrence in endocrine-treated breast cancer patients is stronger.

Adult↗
PubMed2005

Evaluation of low-dose venlafaxine hydrochloride for the therapy of hot flushes in breast cancer survivors.

OBJECTIVE: To evaluate the efficacy and tolerability of long-term treatment with venlafaxine at low dose for the reduction of vasomotor symptoms in breast cancer survivors. DESIGN: Forty consecutive breast cancer patients suffering troublesome hot flushes have been treated for 8 weeks with venlafaxine XR 37.5 mg/day in an open-label study. Vasomotor symptoms have been evaluated before starting treatment and every 4 weeks with a hot flushes diary pointing out the number and the severity of vasomotor symptoms. A Beck Depression Inventory (BDI) was completed at baseline and at the end of the treatment. RESULTS: Thirty patients had completed the first 4 weeks of treatment, reporting a reduction of hot flushes frequency of 39% as compared to baseline (p<0.001). After 8 weeks of treatment, a further significant reduction was observed both for the hot flushes frequency (-53%; p<0.001) and for the hot flushes score (-59%; p<0.001), a measure which reflects both the number and the severity of hot flushes. Very few side effects were reported, mostly nausea in the first 2 weeks of assumption and mouth dryness. Only 23 women had completed BDI at week 8; a reduction of 23% was observed (p=0.000). CONCLUSION: Venlafaxine is an effective treatment for the relief of vasomotor symptoms in patients previously treated for breast cancer. A favourable effect is maintained also in those patients using tamoxifen as adjuvant therapy. The use of the low dose (37.5 mg/day) is associated with minimal side effects and produces a good improvement in hot flushes if pursued over 8 weeks.

Adolescent↗
PubMed2005

The influence of hormone replacement therapy on the pathology of breast cancer.

AIM OF THE STUDY: To assess whether the pathological characteristics of breast carcinomas arising in post-menopausal women who ever used hormonal replacement therapy (HRT) differ from those of post-menopausal patients who never used HRT. MATERIALS AND METHODS: Six hundred and forty three consecutive breast cancer patients were entered in a case control-study. Cases were represented by 111 breast cancer patients who had used or were using HRT at the time of diagnosis, while the remaining 532 patients who never used HRT were chosen as controls. RESULTS: Tumour diameter was smaller in HRT users (17.6 vs 22.1 mm; p=0.002) and tumours of lobular histology were almost twice more frequent among HRT users as in 'never users' (21 vs 12%; p=0.01). No differences were found in grading, hormonal receptor status and axillary nodal status. The expression of c-erb B-2, p53, Ki67 and PS2 measured by immunohistochemistry was similar in the two groups. CONCLUSIONS: Our findings suggest that HRT use may modify the pathological presentation of breast cancer. Further studies are indicated, while other clinical-pathological characteristics did not differ according to HRT use.

Aged↗
PubMed2004

Management of risk of breast carcinoma in postmenopausal women.

Breast carcinoma is the most frequent tumor in the female population. Many factors can influence the risk of breast cancer; some of them, such as old age and breast cancer 1/2 (BRCA1/BRCA2) gene mutations, are associated with a fourfold increase in risk. A previous diagnosis of atypical ductal or lobular hyperplasia or having a first-degree relative with a carcinoma are factors associated with a two- to fourfold increase in risk. A relative risk between 1 and 2 is associated with longer exposure to endogenous hormones as a result of early menarche, late menopause and obesity, or with recent and prolonged use of hormone replacement therapy (HRT) or with behavioural factors such as high alcohol and fat intake. Is it possible to modify breast cancer risk in postmenopausal women? Risk factors related to lifestyle can be changed, even if it is not clear whether modifying these behavioural factors during the postmenopausal period will influence the overall breast cancer risk. For instance, the influence of exogenous hormones throughout life (both oral contraceptives and HRT) should be evaluated according to the individual risk-benefit ratio. The problem is even more complex for women who carry genetic mutations and for those who have close relatives with breast cancer, who may be candidates for risk reduction strategies. Prophylactic bilateral mastectomy is still controversial, but is frequently offered to or requested by this group of women and may be indicated in BRCA1/BRCA2 carriers. Chemoprevention with tamoxifen and with the new selective estrogen receptor modulators, namely raloxifene, is very promising and deserves a thorough discussion for all high-risk women.

Anthropometry↗
PubMed2003

Sentinel node dissection as definitive treatment for node negative breast cancer patients.

AIMS: Negative sentinel node may predict tumour-free axillary nodes in breast cancer. We report the performance of sentinel node dissection at our Institution. METHODS: We analysed data from 212 consecutive women with primary invasive breast tumours less than 3 cm in diameter and no axillary lymphadenopathy who underwent radioguided sentinel node dissection by means of 99mTc-colloidal albumin between 1999 and 2002. Completion axillary node dissection was performed if sentinel nodes contained metastases or if no sentinel nodes were identified. RESULTS: Sentinel nodes were identified in 207/212 of the patients. Fifty-seven patients had tumour-positive sentinel nodes. Only tumour diameter showed significant association with sentinel node status (p<0.000). Per-operative histologic evaluation had a sensitivity of 67.3% and a negative predictive value of 90.4%. No subset of sentinel node positive patients was identified for whom axillary node dissection could be safely avoided. No recurrences were detected at a median follow-up of 15 months. CONCLUSION: Radioguided sentinel node dissection offers a reliable way to assess nodal status in most breast cancer patients. In our experience, both preoperative lymphoscintigraphy and intraoperative histologic evaluation add useful information to the procedure.

Adult↗
PubMed2003

Sentinel node biopsy for breast cancer: yes, less surgery is better surgery.

Breast surgery evolves towards always more precise, but less invasive techniques. The halstedian concept of radical surgery has been abandoned and the majority of patients are now allowed to preserve their breasts provided they receive radiation therapy after surgery. In many institutions standard axillary lymph-node dissection is being replaced by the less invasive and probably also more accurate staging technique known as sentinel-node dissection. Nevertheless, the procedure requires interdisciplinary collaboration and rigorous quality control monitoring to provide optimal results. Many issues, some of which will be discussed in the light of our personal experience, still need to be tested in clinical controlled trials.

Age Factors↗
PubMed2002

The androgen-regulated gene human kallikrein 15 (KLK15) is an independent and favourable prognostic marker for breast cancer.

Many kallikrein genes were found to be differentially expressed in various malignancies, and prostate specific antigen (encoded by the KLK3 gene) is the best tumour marker for prostate cancer. Prostate specific antigen has recently been shown to be an independent favourable prognostic marker for breast cancer. KLK15 is newly discovered kallikrein gene that is located adjacent to KLK3 on chromosome 19q13.4. KLK15 has 41% similarity to KLK3 and the encoded protein, hK15, can activate pro-prostate specific antigen. We studied the expression of KLK15 by real-time quantitative reverse transcriptase-polymerase chain reaction in 202 tissues from patients with breast carcinoma of various stages, grades and histological types. KLK15 expression was found to be a significant predictor of progression-free survival (hazard ratio of 0.41 and P=0.011) and overall survival (hazard ratio of 0.34 and P=0.009). When all other known confounders were controlled in the multivariate analysis, KLK15 retained its prognostic significance. Higher concentrations of KLK15 mRNA were found more frequently in node negative patients (P=0.042). No association was found between KLK15 expression and any other clinicopathological variable. Further, KLK15 is an independent prognostic factor of progression-free survival and overall survival in the subgroup of patients with lower grade and those with oestrogen receptor and progesterone receptor negative tumours in both univariate and multivariate analysis. KLK15 levels of expression were slightly higher (although not statistically significant) in the oestrogen receptor negative and progesterone receptor negative subgroups of patients. KLK15 is up-regulated by androgens in breast cancer cell lines. Time-course and blocking experiments suggest that this regulation is mediated through the androgen receptor.

Adult↗
PubMed2002

Quantitative analysis of human kallikrein gene 14 expression in breast tumours indicates association with poor prognosis.

KLK14 (formerly known as KLK-L6) is a recently identified member of the human kallikrein gene family. This family harbours several genes aberrantly expressed in various cancers as well as established (PSA/hK3, hK2) and potential (hK6, hK10) cancer markers. Similar to other kallikrein genes, KLK14 was found to be regulated by steroid hormones, particularly androgens and progestins, in breast and ovarian cancer cell lines. Preliminary studies indicated that KLK14 is differentially expressed in breast, ovarian, prostatic and testicular tumours. Given the above, we determined the prognostic significance of KLK14 expression in breast cancer. We studied KLK14 expression in 178 histologically confirmed epithelial breast carcinomas by quantitative reverse transcription-polymerase chain reaction and correlated with clinicopathological variables (tumour stage, grade, histotype etc.) and with outcome (disease-free survival and overall survival), monitored over a median of 76 months. KLK14 mRNA levels ranged from 0 to 1,219 arbitrary units in breast cancer tissues, with a mean+/-s.e. of 136+/-22. An optimal cutoff value of 40.5 arbitrary units was selected, to categorise tumours as KLK14-positive or negative. Higher concentrations of KLK14 mRNA were more frequently found in patients with advanced stage (III) disease (P=0.032). No statistically significant association was found between KLK14 and the other clinicopathological variables. KLK14 overexpression was found to be a significant predictor of decreased disease-free survival (hazard ratio of 2.31, P=0.001) and overall survival (hazard ratio of 2.21, P=0.005). Cox multivariate analysis indicated that KLK14 was an independent prognostic indicator of disease-free survival and overall survival. KLK14 also has independent prognostic value in subgroups of patients with a tumour size </=2 cm and positive nodal, oestrogen receptor and progestin receptor status. We conclude that KLK14 expression, as assessed by quantitative reverse transcription-polymerase chain reaction, is an independent marker of unfavourable prognosis for breast cancer.

Adult↗
PubMed2002

Intramuscular depot medroxyprogesterone versus oral megestrol for the control of postmenopausal hot flashes in breast cancer patients: a randomized study.

BACKGROUND: Hot flashes are frequent in postmenopausal breast cancer patients, especially when treated with tamoxifen. Estrogen replacement therapy is the most effective treatment for hot flashes, but its use is controversial in breast cancer survivors. Progestins may offer a good alternative for the control of hot flashes in this setting; in particular, oral megestrol acetate has been proven effective in a randomized, placebo-controlled clinical trial. With the aim of further improving these results, we have designed a randomized study comparing oral megestrol acetate with depot intramuscular (i.m.) medroxyprogesterone acetate (MPA) for the control of hot flashes in postmenopausal patients with a history of breast cancer. PATIENTS AND METHODS: Seventy-one postmenopausal patients were randomized to receive an i.m. injection of depot MPA 500 mg on days 1, 14 and 28, or oral megestrol acetate 40 mg daily for 6 weeks. Patients recorded daily the number and severity of their hot flashes; response was defined as a > or =50% decrease in the number and severity of hot flashes. RESULTS: At week 6, hot flashes were reduced by 86% on average in the whole group of patients, without significant differences between the two progestins. Response was obtained by 75 and 67% of patients receiving MPA or megestrol, respectively (P = 0.5). Responders were followed to assess maintenance of response (without further treatment), which was significantly better with i.m. MPA: in this group, 89% of responders still showed a benefit at week 24, compared with 45% in the megestrol group (P = 0.03). CONCLUSIONS: Our study shows that a short cycle of i.m. depot MPA injections provides significant and long-lasting relief from postmenopausal hot flashes in patients with a history of breast cancer, offering an alternative to estrogen replacement therapy or prolonged administration of oral megestrol.

Administration, Oral↗
PubMed2001

Breast cancer and hormone replacement therapy: putting the risk into perspective.

Data on hormone replacement therapy and breast cancer risk come from a number of observational studies (mostly American studies). Those published up to 1995 were reanalyzed by the Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC). They involved populations where exceedingly high estrogen doses were used as first-line therapy, and a progestin was added in a minority of women. Overall, the CGHFBC reanalysis found that the relative risk increased by 0.023 for each year of use (with an absolute excess risk of two or six cases out of 1000 women treated for 5 or 10 years, respectively). Further American studies, published in 2000 and involving populations where lower doses were used, showed a risk increase of 0.01 per year of estrogen-only use. Both the CGHFBC reanalysis and the further studies did not find an increase of risk in treated overweight women. Possibly, overweight women already have a maximal estrogenic stimulus on the breast due to extraglandular estrogen production. An additional explanation could be that oral estrogens, through their hepatocellular effects, reverse some biological features of obesity (e.g. decreased sex hormone binding globulin level and increased insulin-like growth factor-I bioactivity) that potentially increase breast cancer risk, so balancing the estrogen stimulation. The CGHFBC reanalysis did not show a substantial difference in breast cancer risk between the majority using estrogen alone and the small minority using estrogen plus progestin. Conversely, Swedish studies and the recent American studies suggest that the risk increase could be higher with the addition of a progestin, compared with estrogen-only use. The biological effect of progesterone/progestins on the breast tissue is controversial. Even if the observed increase in risk could be partially ascribed to non-progesterone-like effects of some progestins (e.g. opposing the hepatocellular effects of oral estrogens) and also (in the American studies) to use-bias, a detrimental action due to progesterone-like effects cannot be excluded. However, the theoretical possibility exists that low doses of oral estrogens, plus a progestin providing progesterone-like effects only, will be shown to be associated with a limited breast cancer risk increase.

Breast Neoplasms↗
PubMed2000

How to manage the menopause following therapy for breast cancer. is raloxifene a safe alternative?

Raloxifene is a selective oestrogen receptor modulator (SERM) that has anti-oestrogenic effects on breast and endometrial tissue and oestrogenic actions on bone, lipid metabolism and blood clotting. In postmenopausal women raloxifene decreases bone turnover and increases bone mineral density, reducing the incidence of vertebral fractures. Unlike tamoxifen, raloxifene does not cause endometrial hyperplasia or cancer, as demonstrated by endometrial monitoring with ultrasonography and biopsy during treatment. Evidence suggests that raloxifene lowers total low-density lipoprotein cholesterol levels behaving like oestrogens, but does not increase high-density lipoprotein cholesterol levels. In randomised clinical trials on postmenopausal women with osteoporosis, raloxifene reduced the risk of newly diagnosed ER-positive invasive breast cancer by 76% during a median of 40 months of treatment. However, raloxifene does not alleviate early menopausal symptoms, such as hot flushes and urogenital atrophy, and may even exacerbate some of them. In conclusion, raloxifene may be an alternative for the prevention of long-term effects of oestrogen deficiency (osteoporosis and heart diseases) in women with previous breast cancer not having hot flushes. For symptomatic patients, the association of raloxifene with different drugs which have demonstrated efficacy in the control of vasomotor symptoms is now under evaluation.

Blood Coagulation Disorders↗
PubMed1999

HRT and breast cancer risk: a clue for interpreting the available data.

Epidemiological and biological data on HRT and breast cancer risk are reviewed. Some aspects deserve consideration. (1) The majority of epidemiological data have been gathered from populations where high estrogen doses (> or = 1.25 mg daily of conjugated estrogens) were used as first line therapy. (2) HRT does not increase the risk in overweight women, even in the series in which a risk increase (in longterm users) is found. This could be as a result of the fact that oral estrogens, through their metabolic and hepatocellular effects, reverse some biological features of obesity (e.g. increased insulin-like growth factor I activity and decreased sex hormone binding globulin level) which potentially increase breast cancer risk, so balancing the estrogen stimulation. (3) The progestin addition seems to increase the risk when the 19 nor-testosterone derivatives are used. These androgenic compounds contrast the metabolic and hepatocellular effects of oral estrogens. To sum up, the possibility does exist that even the longterm use of oral estrogens at the right ('low') dose, with the addition of a non-androgenic progestin, will be shown to be associated with a very limited breast cancer risk increase.

Body Weight↗
PubMed1999

HRT, breast and endometrial cancers: strategies and intervention options.

The demand for hormone replacement therapy (HRT) by women who enter the menopause is rapidly increasing in all developed countries. The concern that HRT may enhance morbidity and mortality from malignant diseases still limits the widespread adoption of hormonal treatments. Overall, epidemiological data on cancer incidence and HRT are reassuring, although long-term or inappropriate therapies may slightly increase the risk of developing malignant diseases. Many commercial hormonal compounds are currently available and the safest HRT regimen with regard to cancer risk must be identified. It is equally important that the best strategies for breast and endometrial surveillance in women commencing HRT be outlined, bearing in mind that the diffusion of hormonal therapies may be halted by unnecessary medical interventions.

Breast Neoplasms↗
PubMed1999

The additionally glycosylated variant of human sex hormone-binding globulin (SHBG) is linked to estrogen-dependence of breast cancer.

Sex Hormone-Binding Globulin (SHBG), the plasma carrier for androgens and estradiol, inhibits the estradiol-induced proliferation of breast cancer cells through its membrane receptor, cAMP, and PKA. In addition, the SHBG membrane receptor is preferentially expressed in estrogen-dependent (ER+/PR+) breast cancers which are also characterized by a lower proliferative rate than tumors negative for the SHBG receptor. A variant SHBG with a point mutation in exon 8, causing an aminoacid substitution (Asp 327-->Asn) and thus, the introduction of an additional N-glycosylation site, has been reported. In this work, the distribution of the SHBG variant was studied in 255 breast cancer patients, 32 benign mammary disease patients, and 120 healthy women. The presence of the SHBG mutation was evaluated with PCR amplification of SHBG exon 8 and Hinf I restriction fragment length polymorphism (RFLP) procedure. This technique allowed us to identify 54 SHBG variants (53 W/v and 1 v/v) in breast cancer patients (21.2%), 5 variants (4 W/v and 1 v/v) in benign mammary disease patients (15.6%), and 14 variants (W/v) in the control group (11.6%). The results of PCR and RFLP were confirmed both by nucleotide sequence of SHBG exon 8 and western blot of the plasma SHBG. No differences in the mean plasma level of the protein were observed in the three populations. The frequency of the SHBG variant was significantly higher in ER+/PR+ tumors and in tumors diagnosed in patients over 50 years of age than in the control group. This observation suggests the existence of a close link between the estrogen-dependence of breast cancer and the additionally glycosylated SHBG, further supporting a critical role of the protein in the neoplasm.

Amino Acid Substitution↗
PubMed1999

Conjugated estrogens and breast cancer risk.

Available epidemiologic data suggest the possibility that the use of oral conjugated equine estrogens (CEE) 0.625 mg/day as a first-choice dose could be associated with a very limited (if any) breast cancer risk increase. Some biological peculiarities of oral CEE back the possibility of a limited detrimental effect on breast tissue, due to either direct or indirect actions. Direct actions. Some experimental findings suggest that the 17 alpha-dihydroderivatives of equilenin and equilin (15% of the CEE components) have a non-estrogenic or even an anti-estrogenic effect on breast tissue. This could partially counterbalance the stimulatory action of the other CEE components. Indirect actions. Oral estrogens, through their metabolic and hepatocellular effects (emphasized by the first liver passage) cause a sharp increase in sex hormone binding globulin (SHBG) level which is followed by a lower quantity of both estrogen and androgen in the free, bioavailable, form. More importantly, they cause a decrease in circulating insulin-like growth factor I (IGF-I) activity, due to both a reduction in IGF-I synthesis by the liver and an increase in IGF-binding protein-1 level. A strong relationship between breast cancer risk and the concentration of circulating IGF-I in premenopausal women has been recently found. Actually, estrogens and IGF-I have a synergistic effect on cell proliferation, and IGF-I is necessary for maximum estrogen-receptor activation in breast cancer cell lines. The possibility does exist that the SHBG level increase and the IGF-I bioavailability decrease, caused by oral CEE, balance the increased estrogen stimulation on breast tissue.

Adult↗
PubMed1998

Insulin-like growth factor I (IGF-I) serum level modifications during transdermal estradiol treatment in postmenopausal women: a possible bimodal effect depending on basal IGF-I values.

The objective of this study was to determine the influence of transdermal estradiol administration on insulin-like growth factor I (IGF-I) serum level in a series larger than those published to date. Thirty-nine postmenopausal women with vasomotor symptoms were studied; blood samples (after overnight fast) were obtained just before and at the 6th month of treatment with transdermal estradiol 0.05 mg/day, and serum levels of IGF-I, growth hormone and sex hormone binding globulin (SHBG) were evaluated. Sixteen of the 39 women did not show variations of IGF-I values (group A), while 11 showed an increase (group B) and 12 showed a decrease (group C) by at least 20% with transdermal estradiol treatment. IGF-I basal levels were higher in group C as compared to group A (p < 0.05) and to group B (p < 0.01), intermediate in group A, and lower in group B. Group C showed a significant increase of SHBG values with transdermal estradiol treatment. Transdermal estradiol seems to induce a bimodal effect on IGF-I serum levels, depending on IGF-I basal values. This could be caused by a different responsivity to estrogen action on the liver (the major site of circulating IGF-I production) and also, possibly, by a different degree in insulin sensitivity changes caused by estrogen.

Administration, Cutaneous↗
PubMed1997

Effect of progestins on IGF-I serum level in estrogen-treated postmenopausal women.

Insulin-like growth factor I (IGF-I) has a role in the whole-body anabolism and promotes both normal and abnormal cell growth in several tissues. Although IGF-I is also synthesized locally at numerous other sites, the liver does constitute the major site of its synthesis, and circulating IGF-I is mainly of hepatic derivation. The production of IGF-I is stimulated by growth hormone (GH), the secretion of which is influenced by circulating IGF-I level through a negative feed-back mechanism. Oral estrogen treatment causes a significant decrease of the IGF-I serum level, probably through a hepatocellular effect due to the first hepatic passage. Treatment with transdermal estradiol (tdE2) at the currently used doses does not cause, on average, substantial variations in the IGF-I serum level. The addition of an androgenic progestin--with strong hepatocellular actions, opposite to those of estrogen--completely reverses the IGF-I decrease induced by oral estrogens, and even causes a trend to IGF-I increase when tdE2 is used. Conversely, the addition of a non androgenic progestin, like dydrogesterone, does not cause interference with the estrogen effect.

Administration, Cutaneous↗