Days Of Tamoxifen Research Articles

Confounding Effects of Tamoxifen: Cautionary and Practical Considerations for the Use of Tamoxifen-Inducible Mouse Models in Atherosclerosis Research-Brief Report.

In recent years, fate-mapping lineage studies in mouse models have led to major advances in vascular biology by allowing investigators to track specific cell populations in vivo. One of the most frequently used lineage tracing approaches involves tamoxifen-inducible CreERT-LoxP systems. However, tamoxifen treatment can also promote effects independent of Cre recombinase activation, many of which have not been fully explored. To elucidate off-target effects of tamoxifen, male and female mice were either unmanipulated or injected with tamoxifen or corn oil. All mice received PCSK9 (proprotein convertase subtilisin/kexin type 9)-AAV (adeno-associated virus) injections and a modified Western diet to induce hypercholesterolemia. After 2 weeks, serum cholesterol and liver morphology were assessed. To determine the duration of any tamoxifen effects in long-term atherosclerosis experiments, mice received either 12 days of tamoxifen at baseline or 12 days plus 2 sets of 5-day tamoxifen boosters; all mice received PCSK9-AAV injections and a modified Western diet to induce hypercholesterolemia. After 24 weeks, serum cholesterol and aortic sinus plaque burden were measured. After 2 weeks of atherogenic treatment, mice injected with tamoxifen demonstrated significantly reduced serum cholesterol levels compared with uninjected- or corn oil-treated mice. However, there were no differences in PCSK9-mediated knockdown of LDL (low-density lipoprotein) receptors between the groups. Additionally, tamoxifen-treated mice exhibited significantly increased hepatic lipid accumulation compared with the other groups. Finally, the effects of tamoxifen remained for at least 8 weeks after completion of injections, with mice demonstrating persistent decreased serum cholesterol and impaired atherosclerotic plaque formation. In this study, we establish that tamoxifen administration results in decreased serum cholesterol, decreased plaque formation, and increased hepatic lipid accumulation. These alterations represent significant confounding variables in atherosclerosis research, and we urge future investigators to take these findings into consideration when planning and executing their own atherosclerosis experiments.

Acute mania in patient under tamoxifen

IntroductionTamoxifen is an antioestrogen agent used in breast cancer treatment. According to some guidelines, this molecular was also proposed for the treatment of acute mania. In fact, Tamoxifen inhibits the intracellular action of the protein kinase C (PKC), which is the direct target in the treatment of mania episodes. Lithium and valproate have also the same action.ObjectivesWe aimed to show the case of an acute mania under an inhibitor PKC treatment and insisted that other studies are recommended.MethodsCase report description and research on medline, pubmed with the keywords: Tamoxifen, Bipolar disorder, protein kinase C,mania.ResultsWe reported a case of a 53-year-old woman with past history of unipolar depression. In 2018 when she was diagnosed with breast cancer. She received antidepressant drugs but she interrupted the treatment after a few months. She was treated for her breast cancer with mastectomy, radiotherapy, and 20 mg per day of Tamoxifen prescribed since Mars 2018. She had been admitted in June 2019 in our department for acute mania. The patient received Tamoxifen as it was prescribed. She was not taking any concomitant medications. No history of drug abuse was reported. Medical examination, laboratory, and radiological investigations did not indicate any medical pathology.ConclusionsIn our case, Tamoxifen had not ovoid the acute mania in spite of its Known anti-manic properties as reported in the literature. Possible neurobiological effect of tamoxifen on the nervous system should be studied to evaluate the safety of this treatment mainly in patients with bipolar disorder.

Which antidepressant agent can be used in patients receiving tamoxifen?

IntroductionDepression is frequently observed in carcinology. Many patients with breast cancer, receiving Tamoxifen, may need antidepressants to treat depression. Tamoxifen is a synthetic non-steroidal antioestrogen metabolized by the cytochrome P450 2D6(CYP2D6) to endoxifen which is the active metabolite of this drug. It was reported that the concomitant prescription of Tamoxifen and some antidepressant agents such as paroxetine and fluoxetine may decrease the anticancer effect of tamoxifen as they may inhibit the CYP2D6 pathway.ObjectivesThe objective of this case was to highlight the particularity of management of depression in patients under tamoxifen.MethodsCase report description of a patient treated with Tamoxifen for her breast cancer and who was admitted for major depression, followed by a literature review.ResultsA 36 –year- old woman, had breast cancer and she underwent a mastectomy followed by chemotherapy. Since September 2016, she received 20 mg per day of Tamoxifen as an antihormonal treatment. In November 2018, she was referred to our psychiatry department for depressive symptoms. The patient was sad, she reported social withdrawal, insomnia, anhedonia, and low self-esteem. She had no history of mania or hypomania. A major depressive episode was diagnosed. We prescribed Escitalopram 10 mg per day with clinical improvement. The psychiatric and oncologic status of the patient was stable after two years under tamoxifen and Escitalopram.ConclusionsThe choice of the adequate antidepressant agent in patients under Tamoxifen remains a challenge and requires a thorough knowledge of drug interactions.

Abstract P2-10-05: PowerPIINC trial: Changes in tumor proliferation index and quality of life with 7 days of preoperative tamoxifen

Abstract BACKGROUND: A decrease in Ki67 has been shown to be a predictor of response to tamoxifen. Previous trials have shown a decreased Ki67 proliferation index in breast tumors with as little as 2 weeks of preoperative tamoxifen. However, shortening the preoperative treatment time in window of opportunity studies increases patient acceptance for trial participation. The POWERPIINC trial examined the effect of 7 days of preoperative tamoxifen on breast tumor proliferation and patient symptoms. METHODS: Adult women with untreated stage I or II invasive breast cancer that was ER positive (>1%) planning on breast surgery with no contraindications to tamoxifen were enrolled. Women received 20mg of tamoxifen for 7 days up to the day of surgery and for 14 days afterwards. Proliferation was assessed by Ki67 immunohistochemistry before and after 7 days of tamoxifen. The proliferation genes from the PAM50 were also assessed by RT-PCR. Symptoms and QOL were assessed by the FACT-ES, MENQoL, and BMQ. RESULTS: 52 women were enrolled, and 44 were evaluable for Ki67. The median age was 58.5 years, and the median tumor diameter was 1.2cm. Most women (73%) were post-menopausal. Most tumors were PR positive (88%). Only 8% of tumors were HER2-positive. The Ki67 decreased by a geometric mean of 40% (95% CI 29%-63%), and 73% (95% CI 57%-85%) of women had tumors with decreased proliferation after 7 days of tamoxifen (p=0.0001 by paired t-test). No correlation was seen between the change in Ki-67 and change in FACT-ES or MENQoL scores. Women reported minimal to no bother from psychosocial or physical symptoms at baseline or on the day of surgery. Expression level of individual proliferation genes did not change after 7 days of tamoxifen. CONCLUSION: Seven days of tamoxifen showed a similar relative decrease in the Ki67 proliferation index as that reported for longer courses. Therefore, short window of opportunity trials can be informative. Citation Format: Cohen AL, Factor RE, Mooney K, Wade M, Serpico V, Salama M, Nelson E, Porretta J, Matsen C, Ostrander E, Bernard P, Boucher K, Neumayer L. PowerPIINC trial: Changes in tumor proliferation index and quality of life with 7 days of preoperative tamoxifen [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-10-05.

POWERPIINC (PreOperative Window of Endocrine TheRapy Provides Information to Increase Compliance) trial: Changes in tumor proliferation index and quality of life with 7 days of preoperative tamoxifen

ObjectivesA decrease in Ki67 during neoadjuvant therapy predicts response to tamoxifen. Previous trials have shown a decreased Ki67 in breast tumors with as little as two or more weeks of preoperative tamoxifen. Shortening the preoperative treatment time in window of opportunity clinical trials makes these trials more attractive to women. POWERPIINC examined the effect of 7 days of preoperative tamoxifen on breast tumor proliferation and patient symptoms. MethodsWomen with untreated stage I/II, ER-positive, invasive breast cancer with no contraindications to tamoxifen were enrolled. Women received 20 mg of tamoxifen for 7 days up to the day of surgery. Proliferation was assessed by Ki67 immunohistochemistry before and after 7 days of tamoxifen. Symptoms and QOL were assessed by the FACT-ES and MENQOL. Adherence was measured by pill counts. Results52 women were enrolled, and 44 were evaluable for Ki67. The median age was 58.5 years, and the median tumor diameter was 1.2 cm. Most women (73%) were post-menopausal. Most tumors were PR positive (88%) and HER2-negative (92%). The Ki67 decreased by a geometric mean of 40% (95% CI 29%–63%), and 73% (95% CI 57%–85%) of women had tumors with decreased proliferation (p = 0.0001 by paired t-test). Adherence to taking tamoxifen during the preoperative period was 100%. Women reported minimal bother from psychosocial or physical symptoms at baseline or on the day of surgery. ConclusionSeven days of tamoxifen showed a similar relative decrease in Ki67 as that reported for longer courses, was acceptable to women, and could be considered for window of opportunity studies.

Aromatase inhibitors decrease radiation-induced lung fibrosis: Results of an experimental study

PurposeIn experimental and clinical trials, tamoxifen (TAM) has been shown to increase radiation-induced lung fibrosis (RILF). Furthermore, aromatase inhibitors (AI) have been shown to be superior to TAM in the adjuvant setting and preclinical data suggest that letrozole (LET) sensitizes breast cancer cells to ionizing radiation in other studies. In this experimental study, we evaluated whether AI have any impact on the development of RILF in rats. Materials and methods60 female wistar- albino rats were divided into 6 groups: Control (group A), RT alone (group B), RT + TAM (group C), RT + anastrozole (ANA group D), RT + LET (group E), and RT + exemestane (EXE, group F). RT consisted of 30 Gy in 10 fractions to both lungs with an anterior field at 2 cm depth. Equivalent doses for 60 kg adult dose per day of TAM, ANA, LET, and EXE were calculated according to the mean weight of rats and orally administrated with a feeding tube. Percentage of lung with fibrosis was quantified with image analysis of histological sections of the lung. The mean score values were calculated for each group. the significance of the differences among groups were calculated using one way ANOVA test and Tukey HSD post-hoc test. ResultsMean values of fibrosis were 1.7, 5.9, 6.7, 2.5, 2 and 2.2 for groups A, B, C, D, E, and F, respectively (p = 0.000). TAM increased RT-induced lung fibrosis but without statistical significance. Groups treated with RT + AI showed significantly less lung fibrosis than groups treated with RT alone or RT + TAM (p = 0.000). RT + AI groups showed nearly similar RT-induced lung fibrosis than control group. ConclusionsIn this study, we found that AI decreased RT-induced lung fibrosis to the control group level suggesting protective effect.

Scap is required for sterol synthesis and crypt growth in intestinal mucosa

SREBP cleavage-activating protein (Scap) is an endoplasmic reticulum membrane protein required for cleavage and activation of sterol regulatory element-binding proteins (SREBPs), which activate the transcription of genes in sterol and fatty acid biosynthesis. Liver-specific loss of Scap is well tolerated; hepatic synthesis of sterols and fatty acids is reduced, but mice are otherwise healthy. To determine whether Scap loss is tolerated in the intestine, we generated a mouse model (Vil-Scap(-)) in which tamoxifen-inducible Cre-ER(T2), a fusion protein of Cre recombinase with a mutated ligand binding domain of the human estrogen receptor, ablates Scap in intestinal mucosa. After 4 days of tamoxifen, Vil-Scap(-) mice succumb with a severe enteropathy and near-complete collapse of intestinal mucosa. Organoids grown ex vivo from intestinal crypts of Vil-Scap(-) mice are readily killed when Scap is deleted by 4-hydroxytamoxifen. Death is prevented when culture medium is supplemented with cholesterol and oleate. These data show that, unlike the liver, the intestine requires Scap to sustain tissue integrity by maintaining the high levels of lipid synthesis necessary for proliferation of intestinal crypts.

A randomized phase II presurgical trial of weekly low-dose tamoxifen versus raloxifene versus placebo in premenopausal women with estrogen receptor-positive breast cancer

IntroductionWe previously demonstrated that 1 or 5 mg per day of tamoxifen (T) given for four weeks before surgery reduces Ki-67 in breast cancer (BC) patients to the same extent as the standard 20 mg/d. Given the long half-life of T, a weekly dose (10 mg per week (w)) may be worth testing. Also, raloxifene (R) has shown Ki-67 reduction in postmenopausal patients in a preoperative setting, but data in premenopausal women are limited. We conducted a randomized trial testing T 10 mg/w vs. R 60 mg/d vs. placebo in a presurgical model.MethodsOut of 204 screened subjects, 57 were not eligible, 22 refused to participate and 125 were included in the study. The participants were all premenopausal women with estrogen receptor-positive BC. They were randomly assigned to either T 10mg/w or R 60 mg/d or placebo for six weeks before surgery. The primary endpoint was tissue change of Ki-67. Secondary endpoints were modulation of estrogen and progesterone receptors and several other circulating biomarkers.ResultsKi-67 was not significantly modulated by either treatment. In contrast, both selective estrogen receptor modulators (SERMs) significantly modulated circulating IGF-I/IGFBP-3 ratio, cholesterol, fibrinogen and antithrombin III. Estradiol was increased with both SERMs. Within the tamoxifen arm, CYP2D6 polymorphism analysis showed a higher concentration of N-desTamoxifen, one of the tamoxifen metabolites, in subjects with reduced CYP2D6 activity. Moreover, a reduction of Ki-67 and a marked increase of sex hormone-binding globulin (SHBG) were observed in the active phenotype.ConclusionsA weekly dose of tamoxifen and a standard dose of raloxifene did not inhibit tumor cell proliferation, measured as Ki-67 expression, in premenopausal BC patients. However, in the tamoxifen arm women with an extensive phenotype for CYP2D6 reached a significant Ki-67 modulation.

Abstract A78: A randomized phase II presurgical trial of weekly tamoxifen versus raloxifene versus placebo in premenopausal women with breast cancer

Abstract Background: The presurgical model is a useful tool to test drug activity on surrogate biomarkers of breast cancer, including proliferation measured by Ki-67. We previously demonstrated that 1 or 5 mg/per day of tamoxifen (T) given for 4 weeks before surgery reduced Ki-67 to the same extent than the standard 20 mg/d. Given the long half-life of T and its metabolites, a weekly dose (10 mg/w) may be worth testing. Raloxifene (R), another SERM, has been shown to reduce Ki-67 in a preoperative setting and to be an effective breast cancer (BC) preventive agent in postmenopausal women. Methods: 125 premenopausal estrogen receptor positive BC patients were randomly assigned to either T 10mg/w or R 60 mg/d or placebo (P) for 6 weeks before surgery in a 2:2:1 ratio. The primary endpoint was tissue change of Ki67. Secondary endpoints were other tissue and circulating biomarkers. Results: The median age was 44, 46, 44 and the median BMI was 23, 22, 22 in the P, R and T group, respectively. Tissue biomarkers (Ki-67, ER, PgR) were not significantly modulated by treatment. Only PgR was modestly down regulated by T and more by R but with not statistically significance. More evident were the effects on the circulating biomarkers. Both SERMs significantly reduced IGF-I/BP-3 ratio (mean change P:0; T:-0.01; R:-0.02; p=0.007) and cholesterol (mean change P: 13.73; T: -10.82; R: -8.96; p<.0001) with no difference between the two drugs. Both T and R modulated significantly fibrinogen level (mean change P: 9.3; T: -14.24; R: -35.88 p=0.002) and in particular R was more effective than T (p=0.034). Antithrombin III showed a significant reduction by treatment vs. placebo (mean change P: -2.28; T: -6.19; R: -6.85; P=0.04). SHBG levels were positively influenced by both T and R (mean change P: -10.21; T: 5.95; R: 6.2; p=0.002). Overall compliance measured with pill count was above 80%. No severe adverse events occurred. Conclusions: Our findings show a lack of effect of both SERMs on breast cancer cells proliferation, possibly due to insufficient doses in premenopausal women with elevated estrogen levels. In contrast, both T at very low dose and R at the standard dose were effective on circulating biomarkers. Interestingly, R was more active than T in reducing fibrinogen level, in line with its safer vascular profile. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A78.

Abstract A54: Combining the rexinoid bexarotene with tamoxifen to prevent ER-negative mammary tumors in MMTV-erbB2 mice

Abstract Background: Retinoids, vitamin A analogues that bind to retinoic acid receptor (RAR), play an important role in regulating cell proliferation and differentiation. Our previous studies demonstrated that related molecules, rexinoids (Bexarotene (LGD1069) and LGD100268), that bind the RXR receptor, suppress but do not totally prevent ER-negative mammary tumorigenesis. Using a transgenic mouse model of ER-negative breast cancer (MMTV-erbB2 mice), our laboratory demonstrated that bexarotene delays but does not totally prevent ER-negative mammary tumorigenesis with minimal toxicity. We hypothesized that bexarotene in combination with the anti-estrogen drug tamoxifen would more effectively prevent the development breast cancer. To test this hypothesis we treated MMTV-erbB2 mice with bexarotene, tamoxifen, or the combination from the age of 3 months to 9 months and monitored the mice for mammary tumors. Methods: Virgin MMTV-erbB2 mice at age of 3 months were used for these studies. A defined diet was used (AIN-76A). Mice were randomized into 4 groups (10 mice per group): 1) Tamoxifen control (Sham pellets) and bexarotene control (sesame oil), 2) Tamoxifen control (Sham pellets) and bexarotene (50mg/kg), 2) Tamoxifen pellets (2.5mg/pellet, 90-day-release) and bexarotene control (sesame oil), 4) Tamoxifen pellets (2.5mg/pellet, 90-day-release) and bexarotene (50mg/kg). Tamoxifen or sham pellets were replaced once after 90 days to deliver 180 days of tamoxifen (from age 3 months to 9 months). Bexarotene or sesame oil control was administered by gastric gavage daily (5 days per week) for 180 days (from age 3 months to 9 months). The mice were observed daily for tumor formation, weights were recorded weekly, and tumors were measured twice a week. Mice were sacrificed when tumor sizes exceeded 1500mm3. Analysis of time to tumor formation (defined as the time to develop a 100mm3 tumor) was the primary endpoint of these studies. Analysis of the expression of mammary tissue biomarkers is ongoing. Results: Bexarotene and tamoxifen as single agents slightly delayed the development of mammary tumors in these mice. However, the combination of bexarotene and tamoxifen was much more effective. By 350 days of age, 100% of the control animals developed mammary tumors, while only 10% of the animals treated with bexarotene and tamoxifen developed mammary tumors. This difference in time to tumor development is highly statistically significant (p <0.05; Generalized Wilcoxon test). These mice are still being followed, and updated results will be presented. We are now conducting biomarker studies to measure the effect of tamoxifen, bexarotene, and the combination on the expression of the erbB2 transgene, the estrogen receptor, and on markers of proliferation (Ki67 and cyclin D1) and apoptosis (cleaved caspase 3). Conclusions: The combination of bexarotene and tamoxifen is highly effective at preventing ER-negative mammary tumors in MMTV-erbB2 mice. These preclinical results suggest that combining a rexinoid with an anti-estrogen drug may be useful to prevent both ER-positive and ER-negative breast cancer in humans. These studies were supported by NIH R01 grants (CA101211) and by a Breast Cancer SPORE grant (P50 CA58183). Citation Information: Cancer Prev Res 2010;3(1 Suppl):A54.

Aromatase inhibitors and radiation-induced lung fibrosis

614 Background: In experimental and clinical trials, tamoxifen (TAM) has been shown to increase radiation-induced lung fibrosis (RILF). Aromatase inhibitors (AI) are superior to TAM in the adjuvant setting, and preclinical data suggest that letrozole (LET) sensitizes breast cancer cells to ionizing radiation. However, poor data are available regarding the toxicity of concurrent use of AI and radiation therapy (RT). In this experimental study, we evaluated whether AI have any impact on the development of RILF in rats. Methods: 60 female wistar- albino rats were divided into 6 groups: control (group A), RT alone (group B), RT + TAM (group C), RT + anastrozole (ANA group D), RT + LET (group E), and RT + exemestane (EXE, group F). RT consisted of 30 Gy in 10 fractions to both lungs with an anterior field at 2-cm depth. Equivalent doses for 60 kg adult dose per day of TAM, ANA, LET, and EXE i.e. 20 mg, 1 mg, 2.5 mg, 25 mg, respectively, were calculated according to the mean weight of rats which was 200 gr and ...

The study of tamoxifen and raloxifene (STAR): Initial findings from the NSABP P-2 breast cancer prevention study

LBA5 Background: The STAR trial was designed to compare raloxifene to tamoxifen in terms of relative effect on invasive breast cancer risk and on other beneficial and detrimental outcomes associated with the use of tamoxifen. Methods: The trial opened on 7-1-1999, and accrual was completed November 4, 2004, with 19,747 women enrolled. To be eligible, a woman had to be postmenopausal with a 5-year predicted breast cancer risk of 1.66% as determined by the modified Gail model. Women were randomized and treated in a double-blinded fashion to receive 5 yr of therapy with either 20 mg per day of tamoxifen or 60 mg per day of raloxifene. The protocol-defined monitoring plan called for a final analysis and release of findings when 327 invasive breast cancer cases had been diagnosed in the total population. The mean age of the population at the time of entry into this trial was 58 yr, and the mean 5-yr risk of breast cancer was 4.04%. 93.5% of the women were white; 51.5% had a hysterectomy before entry into the study; 9.2% had a history of LCIS; 71.1% had at least one first-degree relative with a history of breast cancer. The average time on the study is 47 months. Results: There was no difference between the treatment groups in terms of effect on invasive breast cancer: 163 cases in women assigned to tamoxifen and 167 in women assigned to raloxifene (RR = 1.02, 95% CI = 0.82–1.27). The risk of invasive uterine malignancies was 40% less in the raloxifene group (36 in women assigned tamoxifen and 23 in women assigned raloxifene [RR = 0.62, 95% CI = 0.35–1.08]). The risk of non invasive breast cancer was less in the tamoxifen group (57 cases in those assigned to tamoxifen and 81 in those assigned to raloxifene [RR = 1.41, 95% CI = 1.00–2.02]). There were no significant differences between the treatment groups for any of the other invasive cancer sites or for cardiac events, osteoporotic fractures, or deaths. There were fewer thromboembolic events in women taking raloxifene than in those taking tamoxifen. Conclusions: Raloxifene is an effective alternative to tamoxifen for reducing the incidence of invasive breast cancer in postmenopausal women at increased risk of developing the disease and is associated with fewer endometrial cancers, deep vein thromboses, and pulmonary emboli. [Table: see text]

Talking about tamoxifen

Thank you for Andrew Herxheimer's thoughtful editorial.1 As the source for his reference to the deepening of the voice associated with tamoxifen use, 2 I feel I should add a personal note to the discussion. First, I wish to modify his statement slightly, to read: ‘The sometimes irreversible deepening of the singing voice that has been reported to occur with long-term use of tamoxifen for breast cancer is an example of a side effect that prescribers, manufacturers, and drug regulators seem to have considered trivial and have not investigated’ [my emphasis]. My own experience, of serious voice problems 2–3 weeks after starting to take 40 mg a day of tamoxifen in 1987, led me to enquire further of other women, in particular members of the charity Breast Cancer Care (then the Breast Care and Mastectomy Association). I found that similar problems had been reported to the then Director, Jinty Blanckenhagen, who had also notified the manufacturer, ICI Pharmaceuticals. However, this side-effect had not made it to the data sheet. So I conducted a small pilot study among readers of the BCMA newsletter, Network. I invited singers to write in if they had noticed any voice changes. Of the 10 who wrote in, seven had noticed changes similar to my own: mainly croakiness and a lowering of pitch. 2 To me this confirmed that my experience was not unique and I imagined that the drug company would wish to know about it. So early in 1992 I wrote to them, with copies to various other bodies such as the Committee on Safety of Medicines, as well as some eminent breast cancer specialists. The result astonished me. I was living in West Sussex at that time, and a senior member of the ICI medical team flew from Macclesfield to Gatwick, accompanied by another member of staff who seemed to have a Public Relations role, to see me in my home. It felt as if the object of this expensive exercise was to persuade me to shut up. This I did not do, but this particular side effect has still not been listed in the British National Formulary. The problem may be partly dose-related, and now the standard dose is 20 mg, not 40 mg. But I believe that the effect is real and that singers should know about it before embarking on tamoxifen treatment, which is only likely to benefit those with ER+ tumours. It is particularly important to mention it in any trials of tamoxifen for ‘prevention’.

Behaviour of vaginal epithelial maturation and sex hormone binding globulin in post-menopausal breast cancer patients during the first year of tamoxifen therapy.

To evaluate the effect of tamoxifen on vaginal epithelial maturation and on oestrogen-related hepatic synthesis, we prospectively studied the karyopyknotic index (KPI), the maturation index (MI), expressed as a percentage of parabasal (MI-1), intermediate (MI-2) and superficial (MI-3) cells, as well as the serum levels of the oestrogen-dependent sex hormone binding globulin (SHBG). Tests were performed at baseline, after 1, 3, 6 and 12 months of therapy in 64 post-menopausal breast cancer patients. Basal KPI ranged from 0 to 9 (mean 1.5 +/- 0.3) and rose 13.5-fold to 21 +/- 2.5 (P = 0.000) after the first 30 days of tamoxifen. Absence of KPI rise was observed in 23% of patients. Pretreatment MI figures 1, 2 and 3 were 56.9 +/- 5.6, 41.7 +/- 5.4 and 1.4 +/- 0.3, respectively, and sharply shifted to the right (P = 0.000) after 1 month of therapy, indicating an increase of vaginal epithelial maturation. At baselines the SHBG mean value was 62.1 +/- 3.3 nmol/l and underwent an increase of 44% (P = 0.000) after 30 days of tamoxifen. All of these observed 1-month modifications remained stable up to the studied 12 months of therapy. Present findings indicate an early and persistent oestrogenic effect of tamoxifen on the vaginal epithelium and the hepatic synthesis of SHBG.

Alternativa en el tratamiento de la mastopatia fibroquística con tamoxifeno

En la clínica de Mastología del Hospital "Teodoro Maldonado Carbo del IESS de Guayaquil, se estudiaron 50 pacientes entre 18 y 53 años, con Mastopatía Fibroquística (MFQ) de Mayo/93 a Abril/94 a las que se les realizó, al inicio del estudio historia clínica completa, examen físico, prolactinemia, ultrasonografía mamaria y a las pacientes de más de 35 años mamografía. Se administró TAMOXIFENO a dosis de 10mg diario por cuatro meses, realizando control clínico, prolac- tinemia y ultrasonografia mamaria a los 4 y 12 meses.