A New Model Including AMH Cut-off Levels to Predict Post-treatment Ovarian Function in Early Breast Cancer: A Prospective Cohort Study.

BACKGROUND: Breast cancer (BC) treatment decreases fertility capacity, but unnecessary fertility preservation procedures in women who would not be infertile after treatment would be a waste of time and resources and could cause the unwarranted exposure of cancer cells to exogenous sex hormones. It has been largely shown that post-treatment ovarian reserve is directly associated with pre-treatment anti-mullerian hormone levels (AMH0). A threshold for AMH0, or a model including AMH0 and patient characteristics that could distinguish the patients who will be infertile after treatments, still needs to be defined. Accordingly, this study was performed to specifically target this high-priority concern. METHODS: Women≤45 years old with newly diagnosed non-metastatic BC were entered in this multicenter prospective cohort study. AMH0 and two-year post-treatment AMH (AMH2) were measured, and hormonal patient features were recorded as well. Receiver operating characteristic (ROC) curve analysis, decision tree (DT), and random forest analyses were performed to find a cut-off point for AMH0 and define a model involving related features for the prediction of AMH2. RESULTS: The data from 84 patients were analyzed. ROC curve analysis revealed that AMH0>3 ng/mL (Area under the curve=0.69, 95% CI: 0.54‒0.84) was the best indicator for predicting AMH2≥0.7 (sensitivity=79%, specificity=60%). The best model detected by DT and random forest for predicting an AMH2>0.7 with a probability of 93% consisted of a combination of AMH0>3.3, menarche age<14, and age<31. CONCLUSION: This combination model can be used to withhold fertility preservation procedures in BC patients. Performing larger studies is suggested to further test this model.

Using a combination of superb microvascular imaging and other auxiliary ultrasound techniques to increase the accuracy of gray-scale ultrasound for breast masses.

BACKGROUND: Breast ultrasound is highly sensitive, but its specificity is not as high for detecting malignant lesions. Auxiliary modalities like elastography, Color and Power Doppler ultrasound are used as adjuncts to yield both a high sensitivity and specificity. Superb microvascular imaging (SMI) is a newer modality with more accuracy for detecting breast lesions. In this study, our goal was to investigate the role of SMI as an adjunct to ultrasound and find a suitable combination model for the evaluation of breast masses. METHODS: In this cross-sectional study, 132 women with 172 breast masses who underwent ultrasound-guided biopsy were included.. The ultrasound features of the lesion, the strain ratio in strain elastography, the number of vessels for each lesion, their morphology and distribution in Doppler and Power Doppler ultrasound and SMI were recorded for each lesion. A vascular score and a vascular ratio were defined. RESULTS: In the histologic examination, 31 lesions (18%) were malignant and 141 lesions (82%) were benign. The vascular score was more accurate than the vascular ratio in all three modalities. The predictive ability of strain ratio was higher than Doppler and Power Doppler ultrasound and SMI. Adding SMI alone to ultrasound increased the specificity from 46.10% to 61.2% and the accuracy from 55.80% to 70.11%. In the combination of ultrasound with other modalities, the best was the combination of ultrasound, strain elastography, and SMI; which yielded a specificity and sensitivity of 100% and 74.4%, respectively. CONCLUSION: Adding SMI and STE modalities as adjuncts to ultrasound lowers the chance of missing malignant lesions and reduces unnecessary biopsies of breast lesions. A study with a larger sample size using this combination model to evaluate the accuracy with greater precision is recommended.

A pilot study of the use of human amniotic membrane as subcutaneous implants in a mouse model: a potential for temporary substitutes in two-stage breast reconstructions.

INTRODUCTION: Breast reconstruction by prosthesis is frequently performed in breast cancer treatments, and a temporary substitute is used in the first step of two-stage operations. AIM: Due to the advantageous biological features of the human amniotic membrane, we aimed to evaluate its use for temporary implants. METHOD: We prepared small spherical implants from human amniotic membranes and inserted them into BALB/c mice's subcutaneous flanks. Then, we compared the bulging they produced, the durability, and the host reaction with implants made from the chorionic membrane, folded membrane patches, and sterile plastic beads. RESULTS: All amionitic cases were healthy throughout the study and only mild inflammation occurred in them. Furthermore, the bulging of the implants was acceptable and faded gradually. However, moderate inflammation was observed in chorionic implant mice, and the bulging disappeared very soon. Finally, the control group had severe inflammation and the beads implant was rejected. CONCLUSION: Our study showed that the human amniotic membrane could represent a safe and valid tool for breast reconstruction, however, further studies on larger animals and more implants are suggested.

Metformin in the management of fibrocystic breast disease: a placebo-controlled randomized clinical trial.

BACKGROUND AND PURPOSE: Fibrocystic disease (FCD) of the breast as a very common health problem in women has estrogen-dependent and proliferative features. No effective management strategy has been validated for this disorder, so far. The anti-hyperglycemic agent metformin has both anti-proliferative and estrogen-suppressing effects. Thus, we investigated metformin as a management strategy for FCD. METHODS: The study was a double-blind placebo-controlled randomized clinical trial. Premenopausal women with FCD according to history, physical exam and ultrasound, who had measurable microcyst clusters on ultrasound (US) were entered the study. Oral placebo and metformin tablets (500 mg) were used twice daily by participants in the intervention and control groups. Size and number of microcyst clusters on US and the subjective pain score were recorded before and after the intervention. RESULTS: 154 participants were randomly allocated into two groups of 77 interventions and 77 controls. The decrease in size of the largest microcyst cluster in each patient and the mean decrease in number of microcyst clusters were not statistically significant (P = 0.310 and P = 0.637, respectively). However, those microcyst clusters which were ≥ 14 mm became significantly smaller after metformin use (P = 0.006). Additionally, in the subset of participants with pain at baseline, a larger proportion in the intervention group experienced at least 50% reduction in pain score (63.8% (30/47) in the intervention vs. 44.2% (19/43) in the placebo groups, P = 0.031). CONCLUSION: Our study showed that metformin might be effective in the management of FCD. Further studies are proposed for confirmation of this subject.

Metformin as a new option in the medical management of breast fibroadenoma; a randomized clinical trial.

BACKGROUND: Fibroadenoma (FA) is the most common benign solid breast mass in women, with no definite method of management. Because fibroadenoma is dependent on female sex hormones and comprises hypertrophic changes at cellular levels, we investigated the effects of metformin (MF), a safe hypoglycemic agent with anti-estrogenic and anti-proliferative properties, in the management of fibroadenoma. METHODS: In this randomized clinical trial study, eligible women with fibroadenomas were assigned randomly to the metformin (1000 mg daily for six months) or the placebo group. Breast physical and ultrasound exam was performed before and after the intervention, and the changes in the size of fibroadenomas were compared in the two groups. RESULTS: Overall, 83 patients in the treatment, and 92 in the placebo group completed the study. A statistically significant difference in changing size between the two groups was observed only in the smallest mass. In the largest FAs, the rate of size reduction was higher in the treatment group (60.2 % vs. 43.5 %); while a higher rate of enlargement was observed in the placebo group (38 % vs. 20.5 %). In the smallest FAs, the rate of the masses that got smaller or remained stable was about 90 % in the treatment group and 50 % in the placebo group. We categorized size changes of FAs into < 20 % enlargement and ≥ 20 % enlargement. The odds ratio (OR) for an elargemnt less than 20% was 1.48 (95 % CI = 1.10-1.99) in the treatment group in comparison with the placebo group; the odds for an enlargement less than 20% was higher in women with multiples fibroadenomas (OR = 4.67, 95 % CI: 1.34-16.28). In our study, no serious adverse effect was recorded, and the medicine was well-tolerated by all users. CONCLUSIONS: This is the first study that evaluates the effect of MF on the management of fibroadenoma, and the results suggest a favorable effect. Larger studies using higher doses of MF and including a separate design for patients with single or multiple FAs are suggested in order to confirm this effect. TRIAL REGISTRATION: This trial (IRCT20100706004329N7) was retrospectively registered on 2018-10-07.

COVID-19 Outbreak and Consequent Delays in Schedules of the Breast Clinic: Effects on Patients' Breast and Emotional Symptoms.

OBJECTIVE: The pandemic of COVID-19 has affected many aspects of life, and emotional symptoms have been reported to worsen during this time. Also, elective visits in the Breast Clinic have been cancelled or postponed based on the priorities defined in local and international guidelines. Our aim was to investigate the effect of these delays on the breast symptoms and emotional status of our patients. MATERIALS AND METHODS: We called patients whose appointments should have taken place between March and May 2020. After asking for their consent to participate in the study, we asked questions about their breast and emotional symptoms and any worsening of these due to cancellation of their schedules because of the COVID-19 outbreak. We also inquired the relation of breast symptoms with news and thoughts about COVID-19, and if the patients or their close relatives or friends had been affected by COVID-19. We compared the worsening of breast symptoms in patients with and without a positive self- or family history of COVID-19. RESULTS: None of the breast or emotional symptoms had significantly got worse in the patients. Also, there was no significant difference between the two groups regarding the changes in their breast symptoms or emotional health. CONCLUSION: We believe that these results might be evidence in favor of the Breast Clinic triage system, which conforms to most international and specifically to our local recommended strategies.

The Effect of Vitamin D Supplementation on Breast Density Changes: A Clinical Trial Study.

The aim of this study was to determine the effect of supplementation with 50,000 IU/monthly vitamin D for 1 yr on breast density in Iranian women. METHODS: This double-blind, placebo-controlled, single center clinical trial was conducted among 400 women aged 40 yr and older. Participants were allocated to 2 groups. Group 1 received vitamin D (Cholecalciferol) 50,000 IU in tablet form, monthly, for 1 yr. Group 2 received vitamin E 400 IU in tablet form, monthly, for the same period of time. Participants had follow-up clinic visits every 6 mo and received an annual mammogram. RESULTS: Final data were evaluated based on 216 and 194 women in the vitamin D and control groups. The mean decrease in mammographic density was -5.01%(95% CI, -9.9% to -0.01%) and -2.34 %(95% CI, -6.84% to -2.15%) in the vitamin D and control groups, respectively. There was no significant association between vitamin D consumption and breast density after 1 yr (OR = 0.7, 95% CI, 0.46 to 1.06; P = 0.1).Similar results were observed when multivariate model of logistic regression analysis was performed. CONCLUSIONS: This study showed that monthly consumption of 50,000 IU of vitamin D supplementation for 1 yr did not affect breast density.

Association of mammographic breast density with dairy product consumption, sun exposure, and daily activity.

Background. Mammographic density is a risk factor, for breast cancer and its association with various factors is under investigation; we carried out a study to assess its relationship with daily dairy intake, sun exposure, and physical activities. Patients and Methods. Women ≥40 years of age were interviewed about habits of dairy product consumption, daily sun exposure and physical activity. Exclusion criteria consisted of history of breast cancer, consumption of calcium and vitamin D supplements, hormone replacement therapy, or renal disease. Mammographic densities were classified according to the classification system of the American College of Radiologists into 4 classes. Results. Overall 703 cases were entered in the study. The mean age was 48.2 ± 6.2 years. The most common and least frequent classes of mammographic density were classes 2 and 4, respectively. There was no significant association between mammographic density and rate of dairy consumption, amount of sunlight exposure, and daily physical activity. Conclusion. Relation of sunlight exposure and intake of milk products with mammographic density need further study, while the subject of physical activity can be evaluated by a systematic review and meta-analysis of the existing literature.

Levels of serum 25-hydroxy-vitamin d in benign and malignant breast masses.

BACKGROUND: The true association between breast cancer and vitamin D is currently under investigation. We compared serum 25-hydroxy-vitamin D levels in women with benign and malignant breast masses and controls. MATERIALS AND METHODS: Levels of vitamin D were measured by electrochemiluminescense. Serum levels >35 ng/ml, 25-35 ng/ml, 12.5-25 ng/ml and <12.5 ng/ml were considered as normal, mild, moderate and severe vitamin D deficiency, respectively. RESULTS: Overall, 364 women were included in the control, 172 in the benign and 136 in the malignant groups. The median serum vitamin D level was significantly lower in breast cancers than controls. Levels were also lower in malignant than benign cases and in benign cases than controls although statistically non-significant. CONCLUSIONS: Multinomial logistic regression analysis showed that severe vitamin D deficiency causes a three-fold increase in the risk of breast cancer while this was not the case for moderate and mild deficiency.

Risk factors and prevalence of vitamin d deficiency among Iranian women attending two university hospitals.

BACKGROUND: Several studies indicated that there is a high prevalence of vitamin D deficiency in Middle East countries. OBJECTIVES: The aim of this study was to determine the prevalence and assess some risk factors of vitamin D deficiency among women attending our clinics in Tehran, the capital of Iran. PATIENTS AND METHODS: Five hundred and thirty-eight women aged 20-80 years were entered in this cross-sectional study from 2011 to 2012. Serum 25-hydroxy vitamin D levels were measured in all participants after recruiting their demographic and anthropometric data and past medical histories. Deficiency was defined as levels less than 35 nmol/L and classified as mild (≥ 25 nmol/L), moderate (12.5-25 nmol/L) and severe (≤ 12.5 nmol/L). RESULTS: The prevalence of vitamin D deficiency was 69%; mild, moderate and severe degrees were seen in %10.4, %38.3, and %20.3 respectively. Analysis of logistic regression shows that age (OR:0.96, CI: 0.93-0.97), menopause (OR: 0.44, CI: 0.21-0.99) and consumption of multivitamin supplements (OR: 2.67, CI: 1.4-5) were independent predictive factors for Vitamin D deficiency. CONCLUSIONS: This study showed a high prevalence of vitamin D deficiency among Iranian women especially in reproductive ages.

Imperfect correlation of mammographic and clinical breast tissue density.

BACKGROUND: Clinicians determine degree of mammographic density based on tissue firmness on breast examination. The study aimed to compare breast density in mammography and clinical breast examination. MATERIALS AND METHODS: Six-hundred sixty three women 40 years of age or older were studied. The breast exam density was graded from 1 to 4 by two expert surgeons and the mammographic parenchymal density by two expert radiologists. Then for practical reasons, grades 1 and 2 were considered as low-density and grades 3 and 4 as high-density. RESULTS: High and low densities were detected in 84.5% and 15.5% of clinical breast examinations and 59.7% and 40.3% of mammographies, respectively. The statistical analysis showed a significant difference between the breast tissue densities in breast examination with those in mammography. CONCLUSIONS: A clinically dense breast does not necessarily imply a dense mammographic picture.

Clinical and ultrasonographic changes of the breast after use of soy isoflavones.

BACKGROUND: Phytoestrogens may be an alternative therapy in control of menopausal symptoms but their definite effects on breast tissue must be determined. Our study aimed to define the clinical and ultrasonographic changes of the breast after use of soy isoflavones in menopausal women. MATERIALS AND METHODS: Menopausal women with hot flashes were randomly grouped as cases and controls and cases received soy isoflavones for 12 weeks. Breast examination (BE) and ultrasonography (US) were done at 0, 6 and 12 weeks. Tenderness and nodularity on BE were graded 1-4 by breast surgeons. RESULTS: There were 30 women in the case and 26 in the control group. The mean age was 51.3 years and the mean age of menopause was 49.2 years. There was no change in the BE and US at 6 weeks in controls. In the case group, 10% had grade 1 tenderness and 13.3% grade 2 tenderness and grade 1 nodularity in BE accompanied with diffuse small cysts in US. At 12 weeks, there was no change in BE and US in the 2 groups. CONCLUSIONS: There was no statistically significant difference in the BE of the 2 groups at 6 and 12 weeks (p value=0.36 and 0.41 for nodularity and tenderness respectively) and in the US results. Although the literature contains many facts concerning PEs and the breast, further prospective studies are needed to identify structural breast changes produced by PEs in order to identify the appropriate dosage and indications of use.