Evaluation of 1294 Female Patients with Breast Pain: A Retrospective Study.

INTRODUCTION: Mastalgia, or breast pain, is one of the most important complaints referred to outpatient clinics. The objective of this study was to evaluate the factors causing mastalgia. All patients who presented to our clinic with complaints of mastalgia were assessed along with their type of mastalgia symptoms, menopausal status, and radiology results. METHODS: A total of 3157 patients with mastalgia complaints visited our clinic between January 2015 and February 2018. Only 1294 of them were retrospectively screened. Age, sex, menopausal (premenopausal, postmenopausal) status, mastalgia type (cyclic, non-cyclic), and imaging findings of the patients were examined. RESULTS: The mean age was 43.8 ± 11.8 (13-86) years, with 453 (35%) patients younger than 40 years and 841 (65%) older than 40. Cyclic mastalgia was found in 207 (16%) patients, and non-cyclic mastalgia was seen in 1087 (84%) patients. A total of 786 (60.7%) patients were premenopausal, and 508 (39.3%) were postmenopausal. Mammography was used in 545 (42.1%) patients; 1190 (92.0%) women had breast ultrasonography. CONCLUSION: Although breast pain is a common symptom in women who are referred to breast outpatient clinics, we concluded that patients who complain of mastalgia should not be afraid of cancer. Despite this and for reassurance, clinical imaging may be necessary to alleviate these patients' suspicions.

PDE5 inhibition eliminates cancer stem cells via induction of PKA signaling.

Cancer stem cells (CSCs) are involved in metastasis and resistance development, thus affecting anticancer therapy efficacy. The underlying pathways required for CSC maintenance and survival are not fully understood and only a limited number of treatment strategies to specifically target CSCs have been identified. To identify novel CSC targeting compounds, we here set-up an aldehyde dehydrogenase (ALDH)-based phenotypic screening system that allows for an automated and standardized identification of CSCs. By staining cancer cells for ALDH activity and applying high-content-based single-cell population analysis, the proportion of a potential CSC subpopulation with significantly higher ALDH activity (ALDHhigh) can be quantified in a heterogeneous cell population. We confirmed high ALDH activity as surrogate marker for the CSC subpopulation in vitro and validated Wnt signaling as an essential factor for the maintenance of CSCs in SUM149 breast cancer cells. In a small molecule screen, we identified phosphodiesterase type 5 (PDE5) inhibition as potential strategy to target CSC maintenance and survival in multiple cancer cell lines. CSC elimination by PDE5 inhibition was not dependent on PKG signaling, and we suggest a novel mechanism in which PDE5 inhibition leads to elevated cGMP levels that stimulate cAMP/PKA signaling to eliminate CSCs.

A Randomized Controlled Multicenter Trial of an Investigational Liquid Nutritional Formula in Women with Cyclic Breast Pain Associated with Fibrocystic Breast Changes.

OBJECTIVE: A randomized, multicenter, controlled double-blind trial was performed in women with cyclic breast pain (mastalgia) associated with fibrocystic breast changes (FBCs) to determine whether a nutritional formula reduced breast pain and/or nodularity. STUDY DESIGN: Women were randomized to receive a specifically designed liquid formulation (n = 93) (1 g gamma-linolenic acid [GLA], 750 µg iodine, and 70 µg selenium) or control formula (n = 95) (without GLA, iodine, and selenium) daily for three cycles. Women recorded breast pain, medications, and menstrual signs daily using interactive voice-response system. Nodularity was determined by physical breast examination. RESULTS: Breast pain scores decreased similarly in the experimental (-32.2%) and control (-33.1%) groups (p = 0.64). Nodularity was reduced in the experimental, but not the control group (p = 0.03). Among women who continued pain medication, the amount was reduced in the experimental group relative to controls (p = 0.02). CONCLUSION: Women with FBC using the formula containing GLA, iodine, and selenium experienced reduced nodularity and in those women who took over-the-counter breast pain medication, a decrease in the quantity of pain medication was observed.

Focal Breast Pain: Does Breast Density Affect the Need for Ultrasound?

RATIONALE AND OBJECTIVES: This study aimed to determine the utility of directed ultrasound and digital mammogram for evaluating focal breast pain in women with different mammographic breast densities. MATERIALS AND METHODS: This institutional review board-approved and Health Insurance Portability and Accountability Act-compliant retrospective study included 413 cases of focal breast pain in 369 women (mean age 53 years). All cases were evaluated with both mammogram and ultrasound and had at least 2 years of imaging follow-up. Exclusion criteria were non-focal, axillary, or radiating pain; palpable or skin changes; pregnancy or lactation; and history of trauma or infection. Breast density, imaging findings, and biopsy results were recorded. Specificity, positive predictive values, and negative predictive values were calculated. RESULTS: Eighteen percent (76 of 413) of cases demonstrated an imaging correlate. Of these, 74% (56 of 76) occurred in dense breasts and 26% (20 of 76) in nondense breasts. Seventy percent (14 of 20) of lesions in nondense breasts were seen with mammography and ultrasound, whereas 30% (6 of 20) were detected only with ultrasound. Of lesions detected in dense breasts, 29% (16 of 56) were seen with mammography and ultrasound, whereas 71% (40 of 56) were detected only with ultrasound. Thirty-one percent (24 of 76) of cases were biopsied, 42% (10 of 24) of which were detected by ultrasound only. No cancer was detected in initial workup. At 2-year follow-up, three women, all with dense breasts, developed cancer in the same quadrant as the initial pain. CONCLUSIONS: Directed ultrasound, when performed in conjunction with digital mammography for the evaluation of focal breast pain in women with nondense breasts, is of low utility and may contribute to unnecessary intervention as a result of incidental findings.

Mioepitelioma maligno recidivante de la mama, una evolución poco frecuente / Recurrent malignant myoepithelioma of the breast, an uncommon progression

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Pseudoangiomatous stromal hyperplasia causing massive breast enlargement.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign mesenchymal proliferative process, initially described by Vuitch et al. We report an unusual case of a 46-year-old woman who presented with a 6-week history of bilateral massive, asymmetrical, painful enlargement of her breasts, without a history of trauma. On clinical examination, both breasts were markedly enlarged and oedematous, but there were no discrete palpable masses. Preoperative image-guided core biopsies and surgery showed PASH. PASH is increasingly recognised as an incidental finding on image-guided core biopsy performed for screen detected lesions. There are a few reported cases of PASH presenting as rapid breast enlargement. In our case, the patient presented with painful, asymmetrical, massive breast enlargement. Awareness needs to be raised of this entity as a differential diagnosis in massive, painful breast enlargement.

A randomized, double-blind, placebo-controlled trial of ormeloxifene in breast pain and nodularity.

BACKGROUND: Breast pain and non-discrete breast nodularity are common in women. METHODS: We did a randomized, double-blind, placebocontrolled trial of oral ormeloxifene 30 mg, a selective oestrogen receptor modulator (SERM) or placebo twice a week for 3 months in 20-50-year-old women with breast pain with or without lumpiness. Women with a discrete benign lump or cancer were excluded from the study. Serial assessments of pain on a visual analogue scale and nodularity grade on a 5-point ordinal Lucknow-Cardiff scale were done. A total of 151 patients were randomly allocated to two interventions using a block size of 4. RESULTS: Of the 151 patients, 121 (active 57, placebo 64) were available for efficacy analysis. The mean pain level showed a systematic downward trend over five visits (F=105.23, p<0.0001) that significantly reduced in the active group compared to that in the placebo group (F=18.66, p<0.0001). The patterns of variation in pain over time for the individual groups differ from the overall mean pattern for the two groups and thus from one another (F=44.43, p<0.0001). Cumulative frequencies of breast nodularity grades during successive visits showed significant improvement (p=0.001) compared to placebo at the end of the third month. The effect of the active drug persisted till the completion (6 months) of treatment (p<0.001). At the last visit, 93.3% of women in the active group had grade 2 or lower nodularity as compared to 71.1% in the placebo group. Oligomenorrhoea alone was reported by 12 patients. CONCLUSION: Ormeloxifene showed significant efficacy for treating breast pain and nodularity.

Common breast problems.

A palpable mass, mastalgia, and nipple discharge are common breast symptoms for which patients seek medical attention. Patients should be evaluated initially with a detailed clinical history and physical examination. Most women presenting with a breast mass will require imaging and further workup to exclude cancer. Diagnostic mammography is usually the imaging study of choice, but ultrasonography is more sensitive in women younger than 30 years. Any suspicious mass that is detected on physical examination, mammography, or ultrasonography should be biopsied. Biopsy options include fine-needle aspiration, core needle biopsy, and excisional biopsy. Mastalgia is usually not an indication of underlying malignancy. Oral contraceptives, hormone therapy, psychotropic drugs, and some cardiovascular agents have been associated with mastalgia. Focal breast pain should be evaluated with diagnostic imaging. Targeted ultrasonography can be used alone to evaluate focal breast pain in women younger than 30 years, and as an adjunct to mammography in women 30 years and older. Treatment options include acetaminophen and nonsteroidal anti-inflammatory drugs. The first step in the diagnostic workup for patients with nipple discharge is classification of the discharge as pathologic or physiologic. Nipple discharge is classified as pathologic if it is spontaneous, bloody, unilateral, or associated with a breast mass. Patients with pathologic discharge should be referred to a surgeon. Galactorrhea is the most common cause of physiologic discharge not associated with pregnancy or lactation. Prolactin and thyroid-stimulating hormone levels should be checked in patients with galactorrhea.