Use Of Tamoxifen Research Articles

Adjuvant endocrine therapy for premenopausal women: risk stratification, type and duration

Updated results from the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) have helped to identify differential value of various adjuvant endocrine therapy strategies in high-risk and low-risk premenopausal early breast cancer. With a median follow-up of 8 years in SOFT, there is now a significant improvement in disease-free survival (DFS) for those assigned to receive 5 years of tamoxifen plus ovarian function suppression (T + OFS) as compared with tamoxifen (T). Further improvement in DFS was observed for those assigned exemestane plus OFS (E + OFS). While the relative treatment effect from the addition of OFS to tamoxifen in the no chemotherapy and prior chemotherapy cohorts in SOFT was similar, larger absolute improvement in DFS was observed with endocrine therapy escalation in the premenopausal cohort who had received chemotherapy. Despite some improvement in DFS in the lower risk no-chemotherapy cohort, the 8-year results for that cohort continue to show a low risk of distant metastases with the use of adjuvant tamoxifen as sole systemic therapy. A small overall survival advantage from the addition of OFS to tamoxifen has now emerged in SOFT, which appears more clinically meaningful in the prior chemotherapy cohort.In the joint analysis of SOFT and TEXT, there is currently no overall survival improvement at 8 years for those assigned E + OFS versus T + OFS, despite a significant reduction in distance recurrences with E + OFS. Assessing absolute improvements in freedom from distant recurrence observed with the different endocrine strategies across the risk spectrum of patients with HER2-negative tumours in SOFT and TEXT, may assist decision-making for premenopausal patients.

Role of Phytochemicals in Cancer Prevention.

The use of synthetic, natural, or biological agents to minimize the occurrence of cancer in healthy individuals is defined as cancer chemoprevention. Chemopreventive agents inhibit the development of cancer either by impeding DNA damage, which leads to malignancy or by reversing or blocking the division of premalignant cells with DNA damage. The benefit of this approach has been demonstrated in clinical trials of breast, prostate, and colon cancer. The continuous increase in cancer cases, failure of conventional chemotherapies to control cancer, and excessive toxicity of chemotherapies clearly demand an alternative approach. The first trial to show benefit of chemoprevention was undertaken in breast cancer patients with the use of tamoxifen, which demonstrated a significant decrease in invasive breast cancer. The success of using chemopreventive agents for protecting the high risk populations from cancer indicates that the strategy is rational and promising. Dietary components such as capsaicin, cucurbitacin B, isoflavones, catechins, lycopenes, benzyl isothiocyanate, phenethyl isothiocyanate, and piperlongumine have demonstrated inhibitory effects on cancer cells indicating that they may serve as chemopreventive agents. In this review, we have addressed the mechanism of chemopreventive and anticancer effects of several natural agents.

The duration of endocrine therapy and breast cancer patients' survival: A nationwide population-based cohort study.

As research progressed, the recommended duration of endocrine therapy for breast cancer patients has been extended from 5 to 10 years. This study aimed to investigate how the duration of endocrine medication and therapy affect survival rate in the real world. By using the National Health Insurance Research Database (NHIRD), this study examined 1002 breast cancer patients newly diagnosed between 2000 and 2005 as research subjects, and conducted follow-up until 2013. Among these subjects, 51 used aromatase inhibitors (AIs), 561 used tamoxifen, and 390 alternated between the use of tamoxifen and AIs. The mean follow-up period in this study was 9.63 years, and the mean duration of taking endocrine medication was 4.04 years. The tamoxifen group had the longest follow-up period (9.87 years), shortest endocrine therapy duration (3.29 years), and best survival rate (86.1%). Patients were divided into 3 groups based on the duration of endocrine therapy: under 2 years, 2 to 5 years, and over 5 years. It was found that patients who received medication for less than 2 years showed the lowest survival rate with statistically significant differences (P < .001). Therefore, the extension of endocrine therapy duration is critical in improving breast cancer patients’ survival rate.

DMD CLINICAL AND BIOMARKERS: P.139Paediatric use of tamoxifen: good safety profile for boys with Duchenne muscular dystrophy and X-linked myotubular myopathy

Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin, a protein that connects the extracellular matrix to the cytoskeleton in muscle fibres. DMD boys develop progressive muscle wasting, leading to cardiac and respiratory failure and premature death. X-linked myotubular (centronuclear) myopathy (XLMTM) is a very severe myopathy characterized by generalized hypotonia from birth and death of most patients before the age of 2. Our recent preclinical data in mice demonstrated that tamoxifen (a drug used against breast cancer) may be helpful for boys with DMD and XLMTM. TAMDMD, a multicentre, randomized, placebo-controlled, phase 3 clinical trial led by Professor Dirk Fischer (Basel, Switzerland) is being conducted in 5 European countries to assess the efficacy of tamoxifen on >100 DMD boys, of which 16 non-ambulant. Dr Talya Dor (Jerusalem, Israel) is conducting an open-label trial on 30 DMD boys, which suggests that tamoxifen is safe and stops motor decline in DMD boys. A clinical trial with tamoxifen for XLMTM is about to be set in both North America and Europe. Tamoxifen is causing excitement in the Duchenne community and many families are giving the drug to their boys on their own. This goes along with concerns about off-label prescription, quality of alternative sourcing and safety of chronic modulation of the estrogen/androgen balance in boys. In the present work we have reviewed more than 30 papers dealing with paediatric usage of tamoxifen, ranging from recognized off-label application for gynecomastia and McCune Albright syndrome to clinical trials for fibrotic disorders and gliomas and to case reports of compassionate use for a variety of life-threatening diseases. By contrast to women treated for breast cancer, the use of tamoxifen seems not linked to serious adverse events in child. No concern was raised as to sexual development in pre- or peri-pubertal boys. Available data suggest that tamoxifen is safe for boys with DMD or XLMTM.

Factors associated with endometrial pathology during tamoxifen therapy in women with breast cancer: a retrospective analysis of 821 biopsies

This study evaluated the factors associated with endometrial pathologies during tamoxifen use in women with breast cancer. This study analyzed 821 endometrial biopsies from women who received tamoxifen for breast cancer. Clinical characteristics were compared according to the presence of endometrial pathology (atypical hyperplasia and cancer). In addition, patients with endometrial polyps were compared with women with normal histology. Among 821 biopsies, atypical endometrial hyperplasia and cancer were diagnosed in 7 women each. Endometrial polyps were found in 173 women, and 634 women presented normal histology. In comparing women with endometrial pathology (atypical hyperplasia and cancer, n = 14) and those without pathology, parity was significantly lower (P = 0.014) and endometrial thickness was significantly higher (P < 0.001) in women with pathology. In addition, abnormal uterine bleeding was more common in the pathology group (P < 0.001). However, age, body mass index, menopausal status, intrauterine device use, history of diabetes mellitus, and duration of tamoxifen use did not differ according to the presence of pathology. In comparing women with endometrial polyps and those with normal endometrium, significant differences were found in parity (P < 0.001), duration of tamoxifen use (P = 0.003), and endometrial thickness (P < 0.001), but not in the presence of abnormal vaginal bleeding. Parity, endometrial thickness, and the presence of abnormal vaginal bleeding, but not age, body mass index, and menopausal status, may be associated with endometrial pathology during tamoxifen use in women with breast cancer. This finding might provide useful information for gynecological surveillance and counseling during tamoxifen treatment.

Is Tamoxifen Use a Factor Affecting Continence in Breast Cancer Patients?

Introduction: Tamoxifen treatment has been shown to reduce the recurrence and mortality rates in hormone receptor-positive breast cancers independent from chemotherapy. This benefit increases with the prolongation of the use of tamoxifen but with increasing side effects. In this study, we aim to evaluate the presence of urogenital symptoms in breast cancer patients on tamoxifen and compare them with those who are not on any hormonotherapy.Materials and methods: This study was performed on patients diagnosed as early-stage breast cancer. The study group consisted of hormone receptor-positive patients given tamoxifen as adjuvant hormonal therapy. The control group consisted of breast cancer patients who had no hormonotherapy. Patients with a complaint of urinary incontinence with onset after tamoxifen usage were evaluated with Urogenital Distress Inventory Short Form (UDI-6), Incontinence Impact Questionnaire Short Form (IIQ-7) and Incontinence Quality of Life Questionnaire (I-QOL).Results: A total of 137 early-stage breast cancer patients were included in this study; 74 estrogen receptor-positive patients on tamoxifen therapy (study group) and 63 hormone receptor-negative patients with no hormonotherapy (control group). The median age was 44 (30-65) years for tamoxifen users and 49 (27-64) years for the control group. The stages of the patients were similar for both groups. 78.4% of the women in the tamoxifen group and 49.2% in the control group were in the premenopausal period. The groups were similar in regard to body mass index and parity. The complaint of urinary incontinence was more frequent in the study group compared to controls (39 (52.7%) vs. 5 (7.9%)). Women with the complaint of urinary incontinence were evaluated with self-reported UDI-6, IIQ-7 and I-QOL forms and the scores were similar for both study and control groups. A statistically significant relation was observed between cigarette smoking and the presence of urinary incontinence. The percentages of smokers were 50% of those with incontinence and 24.7% of those without incontinence.Conclusion: Urinary incontinence is positively correlated with tamoxifen usage in early-stage breast cancer patients.

Oral lesions and associated factors in breast cancer survivors.

To evaluate the prevalence of oral lesions (OL) and associated factors among survivors of breast cancer (BC). A cross-sectional study involving 150 BC survivors was conducted at a public hospital in southern Brazil. Data were collected on socioeconomic aspects, treatment characteristics and oral problems. The decayed, missing and filled teeth index and the occurrence of OL were evaluated. Logistic regression was performed to determine independent variables associated with the outcome. 24% of the women had at least 1 OL and 33.3% of these had more than one lesion. Melanotic macule was the most prevalent lesion. Duration of tamoxifen use, radiotherapy, missing teeth and xerostomia were associated with the occurrence of OL (P<.05). In the adjusted analysis, women with more than 13 missing teeth and xerostomia had 2.39-fold (95% confidence interval [CI], 1.06-5.40) and 2.71-fold (95% CI, 1.14-6.42), respectively, greater odds of exhibiting OL. Approximately 1/4 of the BC survivors exhibited OL, which were associated with tooth loss and xerostomia. These findings could assist in the establishment of oral health strategies for women with BC.

Endometrial cancer: modern concepts of screening

Currently endometrial cancer remains a pressing issue for public health worldwide. Every year there is a steady increase in morbidity rates, which is associated with an increase in the prevalence of risk factors for the disease among which “non-steroid triad” is prevalent: obesity, diabetes, metabolic syndrome. Other significant risk factors for endometrial cancer include the long-term use of tamoxifen and the presence of Lynch syndrome, which makes it possible to carry out selective screening of the disease in these groups of patients. Endometrial cancer is a symptomatic disease, the main clinical manifestation of which is the bleeding from the genital tract on the background of postmenopause. In this case, with timely diagnostic measures, the disease is diagnosed in more than 80% of cases in the early stages of the tumor process, in which the results of treatment are satisfactory. However, despite years of research, questions remain about the relevance and feasibility of population and selective screening for uterine cancer, the ultimate goal of which is to reduce mortality from this disease in a population. Endometrial biopsy and ultrasound of the pelvic organs are considered as the main screening methods, however, the effectiveness of these methods as a population screening is limited. Unreasonable tests lead to overdiagnosis of the disease, invasive interventions increase the risk of the development of predictable complications. This review of the literature contains current information on factors that increase and decrease the risk of endometrial cancer and the results of scientific research on endometrial cancer screening. This information will allow the doctor to choose a rational tactic for managing each particular patient with various risk factors for endometrial cancer and to avoid unnecessary invasive interventions.

Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer

To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer. Genome-wide association study. Not applicable. Premenopausal women ≤45years of age enrolled in one of these three trials were included if they had at least one menstrual case report form after chemotherapy ended and if they were of European ancestry. Forms during and up to 3months after receipt of GnRH agonist were excluded. None. The association of single-nucleotide polymorphisms with post-chemotherapy menstruation adjusted for trial and arm, age, tamoxifen use, and nodal status. The median age of the 1,168 women was 41years (range 19-45). Among these, 457 (39%) never resumed menses after chemotherapy. Older age, tamoxifen use, and node-negative disease were associated with increased risk of CRA. Adjusting for these, rs147451859, in an intron of PPCDC (phosphopantothenoylcysteine decarboxylase), and rs17587029, located 5' upstream of RPS20P11 (ribosomal protein S20 pseudogene 11), were associated with post-chemotherapy menstruation. Genetic variation may contribute to risk of CRA. Better prediction of who will experience CRA may inform reproductive and treatment decision making in young women with cancer.

Younger tamoxifen-treated breast cancer patients also had higher risk of endometrial cancer and the risk could be reduced by sequenced aromatase inhibitor use: A population-based study in Taiwan.

Objective:Previous Western studies reported that older (≥50 years) breast cancer survivors with tamoxifen treatment had higher risk of endometrial cancer. This study aims to disclose whether younger (<50 years) tamoxifen-treated breast cancer patients also had higher risk of endometrial cancer and to examine whether sequenced aromatase inhibitor (AI) use could reduce the risk.Materials and Methods:A population-based cohort of 39,216 newly diagnosed breast cancer patients was identified from Taiwan National Health Insurance Database from 1999 to 2012. The risk of endometrial cancer in nonusers (n = 14,588), tamoxifen-only (n = 19,302), and sequenced AI (n = 5326) users was compared with Cox regression analysis and was adjusted with age, diabetes, hypertension, and chemotherapy.Results:During the 14-year study period, 133 patients were diagnosed with subsequent endometrial cancers. Compared with nonusers, tamoxifen-only users had higher risk of endometrial cancer (14-year incidence 1.7% vs. 0.3%; adjusted hazard ratio [HR] 3.90; 95% confidence interval [CI], 2.37–6.42). This was observed in both older (≥50 years) and younger (40–50 years) age groups. Adjusted HR (95% CI) for the latter was 3.74 (1.65–8.48). This risk persisted after cessation of tamoxifen use. The risk of endometrial cancer was lower in sequenced AI when compared with tamoxifen-only users (adjusted HR 0.43; 95% CI, 0.25–0.72).Conclusions:Not only patients ≥50 years but also younger (40–49 years) patients with tamoxifen treatment had higher risk of subsequent endometrial cancer in this nation-wide cohort. We suggest regular gynecologic monitoring not only during active use but also during follow-up phase. Sequenced AI use may reduce the risk of endometrial cancer in tamoxifen-treated breast cancer patients.

BMI is an independent prognostic factor for late outcome in patients diagnosed with early breast cancer: A landmark survival analysis

BMI is an independent prognostic factor for late outcome in patients diagnosed with early breast cancer: A landmark survival analysis

Tamoxifen administration in pregnant mice can be deleterious to both mother and embryo.

Since it was introduced 20 years ago, tamoxifen-inducible genetic recombination in vivo has become a standard tool in many fields. This technique has great utility, allowing precise temporal and spatial gene recombination mediated by expression of a Cre recombinase-oestrogen receptor hormone binding domain fusion protein. It is frequently used in developmental biology, either for accurate spatio-temporal gene deletion or for lineage-labelling. Administration of high doses of tamoxifen can rapidly induce abortion in pregnant mice but this can be partially overcome by progesterone co-administration. However, administration of tamoxifen to pregnant mice early in pregnancy may have potentially lethal effects on the mother independently of abortion, and can also severely perturb embryonic development. Despite this, only a few published studies mention this fact in passing, and standard parameters for successful or unsuccessful use of tamoxifen in pregnant mice have not been reported. Therefore, in the interests of providing a framework for more humane animal research, we describe our experiences of tamoxifen administration during early gestation in mice. These observations should assist the design of future studies in accordance with the principles of the three Rs (Replacement, Reduction and Refinement of Animals in Research).

Use of Transvaginal Ultrasound in the Evaluation of Endometrial Pathology in Women with a History of Tamoxifen Use and Postmenopausal Bleeding

Use of Transvaginal Ultrasound in the Evaluation of Endometrial Pathology in Women with a History of Tamoxifen Use and Postmenopausal Bleeding

Anti-Müllerian hormone as a new marker of the ovarian reserve function preservation by goserelin during (neo)adjuvant chemotherapy for young breast cancer patients

To observe the dynamic change of anti-Müllerian hormone (AMH) in 1 year after chemotherapy which is the best biochemical marker of ovarian reserve in reproductive medicine setting and to evaluate the effect of gonadotropin-releasing hormone agonist (GnRHa)goserelin to prevent ovarian reserve function during (neo)adjuvant chemotherapy for young breast cancer patients. Between December 2015 and June 2017, 101 breast cancer patients of age ≤ 45 years with stages I to III had been enrolled. The patients were assigned without interference to receive either (neo) adjuvant chemotherapy with goserelin (goserelin group) or without goserelin (chemotherapy group) as their own selection. AMH and menstrual status were evaluated before, during and 0.5 year, 1 year after chemotherapy. Primary end point was the incidence of low AMH value (<0.4 μg/L) at the end of 1 year. Secondary end point was the incidence of amenorrhea (the absence of menses in the preceding 12 months after assignment). In the study, 51 patients chose to join the chemotherapy group, while the other 50 patients selected goserelin to preserve their ovarian reserve function. More unmarried or childless, hormone receptors negative,receiving breast conservation therapy patients with earlier stage selected goserelin before chemotherapy. The incidence of low AMH value was significantly higher in chemotherapy group than in goserelin group (74.5% vs. 38.0%, P<0.001) in 1 year after chemotherapy. The incidence of amenorrhea was consistent with AMH (56.9% vs. 24.0%, P=0.001). And more patients' menstruation (78.9% vs. 54.5%) and AMH value (71.0% vs. 53.8%) recovered in goserelin group within 6 months after chemotherapy. In subgroup analysis, AMH and menstruation seemingly recovered more in goserelin group independent of age, chemotherapy regimen and use of tamoxifen. Especially, AMH value of 36.4% (8/22) patients in chemotherapy group and 18.4% (7/38) patients in goserelin group still maintained low level (<0.4 μg /L) although their menstruation had recovered 1 year after chemotherapy. In addition, 41 patients (20 patients in chemotherapy group, 21 patients in goserelin group) could be evaluated for the dynamic change of AMH and menstrual status during chemotherapy. The mean level of AMH in chemotherapy group declined rapidly to very low level before the 3rd cycle, while 70% of the patients kept presence of menstruation. At the same time, the mean level of AMH in goserelin group was still above 0.4 μg /L, but all of the patients had menopause. Our study has offered evidence that Goserelin with chemotherapy could protect against ovarian reserve failure for young breast cancer patients, now that more patients' AMH value recovered earlier who had selected co-treatment. AMH may be a more precise marker than menstrual status to clinically evaluate ovarian reserve function pre-, during and post- chemotherapy.

Long-Term Use of Tamoxifen Is Associated With a Decreased Subsequent Meningioma Risk in Patients With Breast Cancer: A Nationwide Population-Based Cohort Study

Background: Earlier studies have indicated a relatively higher risk of occurring meningioma among female breast cancer survivors and have suggested that tamoxifen might decrease this risk. The present study evaluated whether tamoxifen use in breast cancer patients can reduce the risk of meningioma. Methods: We designed a population-based cohort study by using data from the National Health Insurance system of Taiwan to assess this issue. Between January 1, 2000, and December 31, 2008, women with breast cancer and of age ≥20 years were included. They were divided into two groups: those who had not received tamoxifen therapy and those who had. The Cox’s proportion hazard regression analysis was conducted to estimate the effects of tamoxifen treatment and the subsequent meningioma risk. Results: We identified a total of 50,442 tamoxifen users and 30,929 non-tamoxifen users. Tamoxifen users had a borderline significantly lower overall risk of meningioma than non-tamoxifen users [adjusted hazard ratio (aHR) = 0.64, 95% confidence interval (95% CI) = 0.40–1.02]. A statistically significant difference was found in those patients with tamoxifen treatment duration longer than 1,500 days (aHR = 0.42, 95% CI = 0.19–0.91) or with cumulative dosage exceeding 26,320 mg (aHR = 0.44, 95% CI = 0.22–0.88). Furthermore, no statistically significant joint effect of aromatase inhibitors and tamoxifen on the occurrence of meningioma among breast cancer patients was seen. Conclusion: Tamoxifen users had a non-significantly (36%) lower risk of developing meningioma than did tamoxifen non-users; however, our data indicated that tamoxifen therapy is associated with a reduced meningioma risk for Taiwanese breast cancer patients receiving long duration or high cumulative dosage treatment with tamoxifen.

Effects of different doses of tamoxifen on the sperm parameters and chromatin quality in mice: An experimental model.

BackgroundTamoxifen (TX) is widely used for the treatment of male factor and idiopathic infertility. It has been shown that TX induces sperm production and so improves male fertility.ObjectiveThis study evaluated the effects of different doses of TX on the sperm parameters and chromatin quality in mice.Materials and Methods In this research, 24 male NMRI mice were divided into three groups including group A: control animal receiving vehicle; group B: the group receiving basal diet and TX 0.4 mg/kg/day; and group C: the group receiving basal diet and TX 0.6 mg/kg/day for 35 days. Thereafter, epididymal spermatozoa were analyzed for standard parameters and nuclear chromatin quality using Aniline Blue (AB) and Toluidine Blue (TB) staining.ResultsThe results indicated that although the TX did not affect the sperm count, motility, and viability parameters, it could elevate the percentage of sperm cells with abnormal morphology and abnormal chromatin at both doses. In addition, in comparison with the control mice, a significant elevation was observed in spermatozoa with residual histones (assessed by AB staining) at high doses of TX.Conclusion Our experimental data in mice suggested that the use of TX for treating male infertility might increase the rates of spermatozoa with abnormal chromatin in a dose-dependent manner.

The effects of adjuvant endocrine therapy on bone health in women with breast cancer.

In women with oestrogen receptor (ER)-positive early breast cancer, oestradiol is important for breast cancer development and progression. Endocrine therapy prevents the deleterious effects of oestradiol in breast tissue by systemically depleting oestradiol concentration (aromatase inhibitors) or preventing its local action in breast tissue (selective oestrogen receptor modulators i.e. tamoxifen), thereby improving oncological outcomes. Use of aromatase inhibitors in postmenopausal women and ovarian function suppression with either tamoxifen or aromatase inhibition in premenopausal women, consequent to systemic oestradiol depletion, exerts detrimental effects on skeletal health. The oestradiol-deficient state causes increased bone remodelling and a negative bone balance. This results in bone loss, microstructural deterioration and bone fragility predisposing to fractures. Similar effects are also seen with tamoxifen in premenopausal women. In contrast, use of tamoxifen in postmenopausal women appears to exert protective effects on bone but studies on fracture risk are inconclusive. The longevity of women with ER-positive breast cancer treated with adjuvant endocrine therapy emphasises the need to mitigate the adverse skeletal effects of these therapies in order to maximise benefit. In general, fractures are associated with increased morbidity, mortality and are a high socioeconomic burden. Whilst the efficacy of antiresorptive therapy in preventing bone mineral density loss in postmenopausal women has been established, further clinical trial evidence is required to provide guidance regarding fracture risk reduction, when to initiate and stop treatment, choice of agent and optimal management of bone health in premenopausal women receiving endocrine therapy. In addition, potential oncological benefits of antiresorptive therapies will also need to be considered.

“Good Risk”: low-risk patients with ductal carcinoma in situ (DCIS) benefit from whole breast radiotherapy after breast conservation surgery (BCS)–long-term follow-up.

e12062 Background: Identification of patients group with low risk DCIS that do not require radiation therapy after BCS is still a challenge. We assessed recurrence rates in patients with „good risk” DCIS with and without radiotherapy after BCS, and subsequently compared our results with the long-term data from RTOG 9804 trial [1]. Methods: Out of 737 patients with DCIS managed between 1996-2011 at the Cancer Center Warsaw, Poland, 400 were treated conservatively. Out of those 133 were classified as „good risk” patients in accordance with RTOG 9804 trial criteria (DCIS &lt; 2.5 cm, mammographically detected, NG1/G2 with margin = &gt; 3 mm). 79 patients received only BCS and another 54 patients were treated with BCS and radiotherapy. Competing risk of recurrence, DFS and OS were calculated for both groups. The results were compared with the long-term observation results of RTOG 9804 trial. Results: The competing risk of recurrence after 10 years in the group treated with BCS and in patients receiving BCS with radiotherapy was 26% and 6% respectively (p = 0.013). 10-year DFS was 58% and 88% (p = 0.02) and OS was 94% and 97% (p = 0.3) respectively. Based on the ASTRO Conference 2018, 10-year recurrence risk without and with radiotherapy in RTOG 9804 trial were 9.1% and 1.7% [1]. In our study in comparison to RTOG 9804 trial results, more patients had DCIS sized 1.1-2.5 cm, excision margins of 3-9 mm and no patient received adjuvant tamoxifen. Conclusions: Similarly to the results of RTOG 9804 trial [1], radiotherapy reduced recurrence rate in “good risk” DCIS, however, in our study the recurrence rate was higher - probably due to difference in risk factors and no tamoxifen use. 1.McCormick B et al. Randomized trial evaluating radiation following surgical excision for “Good Risk” DCIS: 12year report from NRG/RTOG 9804. ASTRO October 21, 2018.

Clinical pharmacogenomic testing impacts therapy decisions and supportive medication choices in breast cancer.

569 Background: Pharmacogenomics, the study of the interaction between the patient’s genome and therapeutic drug response, evaluates the associations between efficacy and toxicity through analysis of drug metabolizing enzymes. As personalized medicine advances to the forefront of cancer care, pharmacogenomics can evaluate the individual’s ability to metabolize key medications in breast cancer treatment including anti-emetics, opioids, and tamoxifen. Women who do not achieve optimal levels of the active metabolites of tamoxifen are at higher risk of recurrence. Patients on chemotherapy who do not respond to anti-emetics can suffer from nausea and vomiting resulting in dehydration and hospitalization. This project evaluates the feasibility and therapeutic impact of real time pharmacogenomics in a selection of patients at the Inova Schar Cancer Institute (ISCI). Methods: An interdisciplinary team was created through the ISCI and the Inova Translational Medicine Institute to implement cheek swab based pharmacogenomic testing in 50 new patients undergoing mastectomy or neoadjuvant chemotherapy for breast cancer. Study patients were assessed for genotypic variability of key CYP enzymes and resulting impact on anti-emetic choices, perioperative pain control, and tamoxifen use. Results: Data was collected in a RedCap database. The 50 women enrolled were ages 28-83. Cheek swabs were performed in clinic and median turn around time was 7 days. 24 distinct genotypes were found in the 50 patients. 20% had abnormal CYP2D6 phenotypes indicating abnormalities in tamoxifen metabolism. 28% of patients had results leading to changes in dose or medication choice of perioperative pain control. 6% of patients had a CYP2D6 ultra-rapid metabolizer phenotype and were given granisetron in lieu of ondansetron. These patients had no documented nausea or vomiting requiring dose adjustments to the treatment plan or medical intervention. 40% of patients had results recommending avoidance of tamoxifen, 75% of which have ER+ breast cancer. 25% of patients had recommended changes to the dose of tamoxifen. Conclusions: Pharmacogenomic testing is feasible and available real-time for immediate use in the clinic. CYP mutations impact treatment decisions in a significant proportion of patients. Individualized treatment plans tailored to pharmacogenomic recommendations can be created in the multi-disciplinary setting and may decrease side effects of treatment and improve efficacy of curative therapy.

Factors associated with endometrial pathology during tamoxifen use in women with breast cancer: a retrospective analysis of 821 biopsies

Factors associated with endometrial pathology during tamoxifen use in women with breast cancer: a retrospective analysis of 821 biopsies