Breast Imaging in Transgender Patients: What the Radiologist Should Know.

Transgender is the umbrella term for individuals whose gender identity and/or gender expression differs from their assigned sex at birth. With the rise in patients undergoing gender-affirming hormone therapy and gender-affirming surgery, it is increasingly important for radiologists to be aware of breast imaging considerations for this population. While diagnostic imaging protocols for transgender individuals are generally similar to those for cisgender women, screening guidelines are more variable. Currently, several professional and institutional guidelines have been created to address breast cancer screening in the transgender population, specifically screening mammography in transfeminine individuals who undergo hormone therapy. This article defines appropriate terminology with respect to the transgender population, reviews evidence for breast cancer risk and screening in transgender individuals, considers diagnostic breast imaging approaches, and discusses special considerations and challenges with regard to health care access and public education for these individuals. ©RSNA, 2019.

Ultrasonographic features and CA125 levels of hormonally active ovarian tumors.

OBJECTIVES: Subjective ultrasonographic assessment is currently considered to be the best method of differentiation between various types of ovarian tumors. The aim of the study was to evaluate selected ultrasonographic features and CA125 levels of hormonally active ovarian tumors. MATERIAL AND METHODS: A total of 1135 women with ovarian tumors were diagnosed between 2006 and 2014 at the Division of Gynecologic Surgery, Poznan University of Medical Sciences. Within these tumors, there were 60 hormone-secreting ovarian tumors, including: 20 granulosa cell tumors, 28 fibrothecomas, 10 dysgerminomas, 2 struma ovarii, and 9 metastatic ovarian tumors. The tumors were evaluated by ultrasonography according to the International Ovarian Tumor Analysis group criteria. Additionally, we evaluated serum CA125 levels in all patients. RESULTS: Granulosa cell tumors occurred most frequently as large unilocular-solid cysts, moderately to highly vascularized, with low-resistance vascularization. Dysgerminomas were predominantly large unilocular-solid cysts or purely solid tumors, with minimal to moderate low-resistance vascularization. Fibrothecomas were solid masses with minimal, high-resistance vascularization. Struma ovarii occurred as small, solid masses with abundant, highresistance vascularization. Metastatic ovarian tumors presented mainly as multilocular-solid tumors with strong, low-resistance vascularization. Papillary projections were most frequently observed in metastatic tumors and granulosa cell tumors in 56% and 50% of the cases respectively, although only half of granulosa cell tumors papillary projections exceeded 3 mm. Elevated CA125 levels were found only in metastatic ovarian tumors. CONCLUSIONS: Hormonally active ovarian tumors present several ultrasonographic features which may facilitate preoperative diagnosis.

Advanced vulvar apocrine carcinoma expressing estrogen receptors that responds to tamoxifen therapy.

Primary vulvar carcinoma is rare and thought to arise from either anogenital mammary-like glands or native apocrine sweat glands. The diagnosis is predominantly based on tumor morphology with supportive evidence from immunohistochemical staining and exclusion of a primary breast carcinoma. The primary modality of treatment is surgery, while optimal managment of advanced disease is unclear. We present the case of a lady who had metastatic recurrent apocrine carcinoma expressing estrogen receptors, who had a complete response assessed by PET-CT scanning after 7 months of tamoxifen therapy. The report includes a discussion of the histological diagnosis and assessment of response to treatment by PET-CT scanning.

[Breast cancer in Mexican women under 40]. / Cancer de mama en mujeres mexicanas menores de 40 años.

BACKGROUND: Breast cancer is the leading cause of death from malignancy in women. The incidence increases with age, but the relationship between age and survival of breast cancer patients is not well defined. It is observed that young women with breast cancer have patterns more aggressive biological. OBJECTIVE: To determine the frequency, sociodemographic, clinical and histopathological features of breast cancer in women under 40 years attending a specialist breast unit in Mexico City. PATIENTS AND METHOD: Transversal, descriptive and retrospective study of patients under 40 years of age with breast cancer treated between 2005 and 2010. RESULTS: 1430 cases were diagnosed with breast cancer five years with a mean age of 53.64 +/- 11.87 years (range 23 to 93 years), 142 cases were women under 40 years of age (10%). The auto-detection of a breast lump was the most frequent clinical manifestation (50%). CONCLUSION: The prevalence of clinical stage III in this age group suggests the difficulty of diagnosis, the high breast density, which is one factor limiting studies of screening with mammography, it diminishes their effectiveness in early detection of breast cancer.

[Letrozole vs. tamoxifen as neoadjuvant therapy for postmenopausal patients with hormone-dependent locally-advanced breast cancer]. / Letrozol vs tamoxifeno como terapia neoadyuvante para pacientes posmenopáusicas con cáncer de mama hormono-dependiente localmente avanzado.

BACKGROUND: Previous studies demonstrated that Letrozole (aromatase inhibitor) and tamoxifen (selective modulator of estrogen receptors) are effective in the treatment of postmenopausal women with locally advanced tumors, stage III and hormone dependent. OBJECTIVE: To present display the complete clinical answer incidence and the complete pathological answer with the use of induction hormonotherapy. METHODS: Put-analysis in 40 patients with breast cancer, to chanalicular infiltrated, eligible were treated in a prospective study, to double blind person, using per os: letrozol, 2.5 mg; tamoxifen, 20 mg, known widely like selective modulator of estrogen receivers; oral route, during 36 consecutive months. Reports at the beginning were taken, subsequent to 3, 6 and 12 months to evaluate the frequency of complete respond. The patients, who did not show answer neoadjuvant therapy, were put under treatment with radiotherapy. The patients who showed good partial pathological respond, or clinical partial respond, went candidates to radical mastectomy. According to the protocol of the study, the patients subsequent to surgery who showed partial pathological respond or complete pathological respond, continued adjuvant handling adyuvant therapy by 2 years consecutive or until the presence of progression of the disease. It was used like statistical method Chi2, with p of Table cloth to evaluate the differences. RESULTS: During a period of 3 years, january of the 2003 to january of the 2005, 2 groups of patients, 40 studied altogether; the age average was of 65,5 years, with a rank of 55 to 75 years with breast cancer, stages: IIA to IIIB. Without complete respond 25% of the group with tamoxifen; 20% with letrozol Those patients happened to radiotherapy. The collateral effects of the use of hormonotherapy with letrozol appeared in a 55% and with the use of tamoxifen in a 60% of the patients with breast cancer (p = 0.5). They did not respond to neoadyuvant therapy (hormonal receptors < to 30%): with letrozol 19% of them and 25% with tamoxifen; reason why they received treatment with radiotherapy. All patients candidates to surgery, were benefitted with the mastectomy handling. CONCLUSIONS: Results although preliminary, suggest that neoadyuvant treatment with hormone-therapy in postmenopausal patients with breast cancer, have good prognosis. Induction therapy, were better tolerated, with greater effectiveness and improved the clinical and objective respond in women with breast cancer in the postmenopausal. Work serves as tool to determine the indication to us of induction hormonotherapy; and identify to those patients with breast cancer, locally advanced in post menopause with better prognosis to be rescued with radical mastectomy. Study needs more background and show the impact of letrozol, as hormonotherapy used in neoadjuvancy, to confirm if relieves period without disease or survives, before mastectomy. In a near future, it shall important to investigate if is useful the radical mastectomy in those postmenopausal patients with complete objective respond, after the use of an aromatase inhibitor.

[Perivascular epithelioid tumors: Utility of the positron emission tomography with 18F-fluorodesoxyglucose (PET-TAC FDG) in their staging and follow-up]. / Tumor epitelioide perivascular uterino. Utilidad de la tomografía por emisión de positrones con (18)F-fluordesoxiglucosa en su estadificación y seguimiento.

Perivascular epithelioid tumors (PEComas) are a rare group of mesenchymal neoplasms with an unpredictable natural history and uncertain malignant potential. Uterine involvement and their association with tuberous sclerosis are typical for these tumors. We present a case of a 40-year old patient who was incidentally diagnosed of a uterine PEComa and serial studies of PET-CT with FDG were performed for staging and therapeutic response assessment. FDG PET-CT proved to be a valuable tool for detecting unsuspected pulmonary metastases and defining the reassessment of the patient after chemotherapy. The findings suggest that since this is a rare tumor, which does not always have benign behaviour, PET-CT may be a useful diagnostic imaging procedure for staging and clinical monitoring of patients who suffer this type of tumors.

Tor Vergata University-Hospital in the Beginning of COVID-19-Era: Experience and Recommendation for Breast Cancer Patients.

COVID-19 has been officially declared as a pandemic by the WHO. Italy was the first European country to be strongly affected by this outbreak. All elective and health promotion activities were reduced. Accordingly, Italian Breast Units and breast cancer (BC) screening programs scaled down significantly their activities. The aim of this study was to evaluate measures that could potentially reduce the clinical impact of COVID-19 on BC patients. Temporary recommendations are needed that could assist specialists in preventing COVID-19 infection and optimizing resources for diagnosis and treatment of BC patients.

Preclinical Molecular Imaging for Precision Medicine in Breast Cancer Mouse Models.

Precision and personalized medicine is gaining importance in modern clinical medicine, as it aims to improve diagnostic precision and to reduce consequent therapeutic failures. In this regard, prior to use in human trials, animal models can help evaluate novel imaging approaches and therapeutic strategies and can help discover new biomarkers. Breast cancer is the most common malignancy in women worldwide, accounting for 25% of cases of all cancers and is responsible for approximately 500,000 deaths per year. Thus, it is important to identify accurate biomarkers for precise stratification of affected patients and for early detection of responsiveness to the selected therapeutic protocol. This review aims to summarize the latest advancements in preclinical molecular imaging in breast cancer mouse models. Positron emission tomography (PET) imaging remains one of the most common preclinical techniques used to evaluate biomarker expression in vivo, whereas magnetic resonance imaging (MRI), particularly diffusion-weighted (DW) sequences, has been demonstrated as capable of distinguishing responders from nonresponders for both conventional and innovative chemo- and immune-therapies with high sensitivity and in a noninvasive manner. The ability to customize therapies is desirable, as this will enable early detection of diseases and tailoring of treatments to individual patient profiles. Animal models remain irreplaceable in the effort to understand the molecular mechanisms and patterns of oncologic diseases.

In vivo measurement of the hypoxia marker EF5 in Shionogi tumours using (19)F magnetic resonance spectroscopy.

PURPOSE: (19)F magnetic resonance spectroscopy (MRS) was used to non-invasively detect EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] adducts in the Shionogi tumour model of prostate cancer to evaluate hypoxia. MATERIAL AND METHODS: (19)F MRS signal of EF5 in Shionogi mouse tumours was acquired using a 2 cm diameter solenoid volume coil with a 7.05 T Bruker scanner. MRS signal was observed in mouse tumours longitudinally following intraperitoneal (IP) injection of EF5. Another mouse group was injected intravenously (IV) with EF5, and in vivo MRS signal was obtained two hours after injection. This data was compared with the ex vivo percentage of hypoxic cells present in the corresponding excised tumours, determined by flow cytometry of bound EF5. RESULTS: Longitudinal (19)F MRS signal attributable to EF5 began to decline within five hours of EF5 administration. Flow cytometry comparisons yielded an inverse correlation (p-value < 0.006) between the MRS signal and tumour hypoxic cell percentage. The tumours exhibited an average cell viability of 34 +/- 26%. CONCLUSIONS: The results confirmed that MRS of EF5 in mice is an unsuitable technique for the determination of EF5 binding as a measure of tumour hypoxia.

Impact of a mammography screening programme on the breast cancer population of the Region of Valencia (Spain).

OBJECTIVE: Randomised clinical trials with a control arm of non-screened patients are nowadays ethically impossible. The aim of this study was to establish the impact of mammography screening on a non-selected population. PATIENTS AND METHODS: Between January 1993 and December 2002, 3662 patients were included, 2313 in the screened group and 1349 in the unscreened group. RESULTS: 55.3% of the screened patients were diagnosed in stage I vs. 26.1% in the non-screened group. The proportion of stage III-IV was 4.6% and 19.8% for the screened and unscreened groups respectively (p<0.001). 48.8% in the screening group were submitted to mastectomy vs. 66.4% of the unscreened patients (p<0.001). Overall survival was superior for the prevalent cases in the screening group, with a relative risk of 0.49, and was not significant for the incident cases. CONCLUSIONS: Diagnosis of breast cancer in the mammography screening programme of the Region of Valencia significantly increases conservative surgery rates and suggests an improvement in survival in prevalent cases. The increased rate of early stages in these patients could be the main reason of this benefit.

18F-Fluoroestradiol.

Estrogen receptor (ER) expression is an important determinant of breast cancer behavior and is critical for response to endocrine therapies such as tamoxifen and aromatase inhibitors. In current practice, ER expression is determined by assay of biopsy material. In more advanced disease, tissue assay may present practical difficulties and be associated with significant sampling error. This and other considerations motivated the development of ER imaging agents for positron emission tomography (PET), of which the most successful has been (18)F-16alpha-17beta-fluoroestradiol (FES). In this review, we highlight aspects of ER biology and the importance of the ER in breast cancer therapy; review the structure and synthesis of FES; describe its kinetics and safety/dosimetry data; and highlight validation studies. Also discussed are early results in patients using FES-PET to localize ER-expressing tumors and associated data pointing toward its accuracy as a predictive assay for breast cancer endocrine therapy. Finally, early data for tumors and sites other than breast cancer are mentioned. Preliminary data strongly point toward potential clinical utility for FES-PET, motivating further validation and future clinical trials with prospective endpoints tested under appropriate regulatory oversight.

A small animal positron emission tomography study of the effect of chemotherapy and hormonal therapy on the uptake of 2-deoxy-2-[F-18]fluoro-D-glucose in murine models of breast cancer.

PURPOSE: We used small animal positron emission tomography (PET) imaging to monitor the time-course of tumor metabolic response to hormone and chemotherapy in a murine model of hormone-sensitive breast cancer. PROCEDURES: Estrogen receptor positive murine mammary carcinomas were inoculated in Balb/c mice. Small animal PET imaging using 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG) was used to assess tumor metabolic activity. Imaging was done before and at days 1, 7, and 14 after the administration of doxorubicin, methotrexate, letrozole, or placebo. The tumor uptake of FDG was calculated from a region-of-interest drawn around the tumor. RESULTS: All treatments resulted in a decrease in tumor growth rate and end volume compared to untreated control. FDG uptake was also markedly decreased after treatment although a flare reaction was observed on PET at day 7, the intensity of which varied according to the treatment modality. CONCLUSION: PET imaging is sensitive to detect early changes associated with therapy in murine breast cancer models. A flare reaction was observed 7 days after the initiation of therapy.

The relationship between FDG uptake in PET scans and biological behavior in breast cancer.

BACKGROUND: Positron emission tomography (PET) is a non-invasive imaging modality used in the diagnosis and staging of breast cancer. However, several factors can affect fluoro-deoxyglucose (FDG) uptake by a tumor. To clarify the parameters that most affect FDG accumulation in tumors, the relationship between standardized uptake values (SUVs) and clinicopathological factors and immunohistopathological analysis was investigated in breast cancer. MATERIAL AND METHODS: PET studies were performed preoperatively on 37 patients with breast carcinoma. SUVs were counted at one hour (early phase) and at two hours (delayed phase) after FDG injection. The relationships between SUVs and 13 clinical, pathological and immunohistchemical factors were studied. RESULTS: A significant association was found between FDG accumulation and early and delayed phase mitotic counts (p=0.0018 and 0.0010, respectively), Ki67 positive cell percentage (p=0.0098 and 0.0062, respectively), and nuclear grade (p=0.0232 and 0.0195, respectively). On the other hand, nodal status weakly correlated with the delayed phase (p=0.0907). However, other clinicopathological parameters and immunohistopathological status, which included tumor size, age, histology, estrogen receptor, progesterone receptor and Her2/neu overexpression, did not correlate significantly with FDG uptake. CONCLUSION: Mitotic count and Ki67 reflect cellular aggressiveness. These parameters were strongly correlated with tracer uptake. Thus our data suggested that the biological behavior of breast cancer is reflected in the variation of FDG uptake by the tumor. However, whether FDG uptake is a true prognostic and predictive factor remains to be confirmed in larger studies over an extended period of time.

[Mediastinal lymph nodes during the course of a metastatic prostate cancer]. / Adenopatías mediastínicas en la evolución de un cancer de próstata metastásico.

Prostate carcinoma is one of the most frecuent cancers in men. Significant numbers of patients have regional lymph node and bone metastases during the course of the disease. Mediastinal lymphadenopathy and cutaneous metastases are uncommon and signify well-advanced disease. We report the case of a patient with prostate cancer who develops mediastinal lymphadenopathy, pulmonary nodules and cutaneous metastases 8 years after the diagnosis.

Bromine- and iodine-substituted 16alpha,17alpha-dioxolane progestins for breast tumor imaging and radiotherapy: synthesis and receptor binding affinity.

Progesterone receptors (PRs) are present in many breast tumors, and their levels are increased by certain endocrine therapies. We describe the synthesis and PR binding affinities of a series of bromine- and iodine-substituted 16alpha,17alpha-dioxolane progestins, some of which, when appropriately radiolabeled, are potential agents for diagnostic imaging of PR-positive breast tumors using positron emission tomography (PET) and for radiotherapy. These compounds were synthesized from halogenated furanyl, phenyl, and thiophenyl aldehydes and a progestin 16alpha,17alpha,21-triol (5) in the presence of HClO4 or Sc(OTf)3 in high yields under optimized conditions. A new reagent, perfluoro-1-butanesulfonyl fluoride (PBSF), was used to convert the C-21 OH to F in high yields. The relative binding affinities (RBAs) of the most promising compounds for the PR (RBA of R5020 = 100) were 16alpha,17alpha-[(R)-1'-alpha-(5-bromofurylmethylidene)dioxyl]-21-hydroxy-19-norpregn-4-ene-3,20-dione (endo-6; RBA = 65 and moderate lipophilicity), 21-fluoro-16alpha,17alpha-[(R)-1'-alpha-(5-iodofurylmethylidene)dioxyl]-19-norpregn-4-ene-3,20-dione (endo-14; RBA = 40) and 21-fluoro-16alpha,17alpha-[(S)-1'-beta-(4-iodophenylmethylidene)dioxyl]-19-norpregn-4-ene-3,20-dione (exo-16; RBA = 34).

Octreotide scintigraphy and Chromogranin A do not predict clinical response in patients with octreotide acetate-treated hormone-refractory prostate cancer.

In this pilot study, the predictive value of Octreotide scintigraphy (Octreoscan) and/or Chromogranin-A (CgA) was investigated in patients with hormone-refractory prostate cancer treated with Octreotide acetate. In total, 20 patients with progressive disease and bone metastases entered the trial. At baseline Octreoscan, CgA, PSA, alkaline phosphates (ALP) and two self-administered questionnaires (EORTC QLQ C-30 (v3) and brief pain index) were performed and a diary of the pharmaceutical was started. The treatment consisted of Octreotide (Sandostatin LAR) acetate 30 mg intramuscular injection every month. The blood samples and questionnaires were repeated every month until 3 months. Clinical responder was defined as a patient with increased global health score more than 10 units and stable or decreased pain score without an increase in analgesic. In all, 17 patients were treated per protocol, and four were assessed as clinical responders. Six patients developed a reduction in ALP (median -26%, range -5 to -78%). All patients increased in PSA. At baseline, three patients had a negative Octreoscan and the patients with positive lesions, demonstrated uptake of low intensity. At baseline the CgA was elevated above the normal range in 15 of the patients, and during treatment five patients decreased their CgA to the normal range. Neither baseline Octreoscan nor CgA could identify the clinical reponders. A minority of patients improves their health-related quality of life. The decrease and normalization of CgA levels in five patients during therapy indicates therapeutic activity but Octreoscan and CgA could not identify clinical responders.

Thyroid cancer presenting as a PET incidentaloma in a patient with concomitant breast cancer metastases to the thyroid.

INTRODUCTION: Metastases to the thyroid gland are considered a rare cause of thyroid tumor. Furthermore, a relationship between breast and thyroid carcinoma has been previously proposed. CASE DESCRIPTION: We describe the case of a 59-year-old woman who presented with simultaneous papillary and breast carcinoma within the thyroid gland. F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) done for the evaluation of her metastatic breast cancer revealed a thyroid incidentaloma with a high metabolic rate (standardized uptake value [SUV] of 13). She underwent thyroidectomy and the pathology revealed papillary thyroid carcinoma corresponding to the lesion visualized on FDG PET. However, small metastatic implants of breast carcinoma were seen within the opposite thyroid lobe. CONCLUSION: This is a rare description of a concomitant papillary thyroid carcinoma presenting as an FDG PET incidentaloma alongside breast cancer metastases to the thyroid gland. Thyroid and breast cancer sometimes occur in the same patient. However, no explanation has been found to link these 2 cancers. Although uncommon, FDG PET thyroid incidentalomas seem to harbor a higher rate of malignancy than incidentalomas found on conventional imaging. In the appropriate clinical setting, it is therefore suggested to investigate these lesions thoroughly.

A fluorine-18 labeled progestin as an imaging agent for progestin receptor positive tumors with positron emission tomography.

The potential of the fluorine-18 labeled progestin 21-[18F]fluoro- 16 alpha-ethyl-19-norpregn-4-ene-3,20-dione [( 18F]FENP) as an imaging agent for the in vivo assessment of progestin receptor (PR) positive neoplasms with positron emission tomography has been investigated. Tissue distribution studies in immature estrogen primed female rats revealed high uptake of radioactivity, expressed as the differential absorption ratio, by uterine tissue. After simultaneous administration with unlabeled FENP, a significant decrease (83%) in uterine uptake was observed 60 min after injection. Uterine uptake was highly selective. The ratio of uptake of radioactivity by uterine tissue to that by blood was 39 at 180 min. In mice bearing transplanted Grunder strain mammary carcinomas tissue, distribution studies demonstrated a selective uptake of [18F]FENP by PR positive tumors. Pretreatment with unlabeled FENP caused a significant decrease (66%) in tumor uptake. Uptake by other tissues was not affected by the presence of unlabeled progestin. The ratio of uptake of radioactivity by tumor tissue to that by blood was 4.7 at 180 min. For FENP pretreated mice and mice bearing PR negative tumors, this ratio was 1.7 and 1.1, respectively. It is concluded that the uptake of [18F]FENP by uterine and by PR positive mammary tumor tissue in vivo is primarily receptor related, presumably to the PR. Furthermore, [18F]FENP appears to be suitable for imaging of PR positive human neoplasms with positron emission tomography.

The prognostic value of sentinel lymph node micrometastases in patients with invasive breast carcinoma.

AIM: The prognostic value of sentinel lymph node micrometastases in invasive breast cancer patients is still widely debated. Even if, in the absence of unequivocal guidelines, the axillary lynphadenectomy is not still performed in the routine clinical care of these patients. METHOD: We have retrospectively analyzed 746 patients with operable invasive breast cancer and clinically negative axillary lymph nodes. These patients underwent conservative surgery or total mastectomy with sentinel lymph node biopsy. Patients with micrometastases in the sentinel lymph node treated with axillary dissection has been checked and the involvement of the remaining lymph nodes analyzed. Patients with micrometastases in the SLN not followed by axillary dissection have been checked as well and the incidence of recurrences has been evaluated in both groups. RESULTS: Micrometastases were found in 51 (6.83%) patients and isolated tumor cells in 8 (1.07%) patients at frozen section and confirmed at the final hystopathologic examination. Fifteen of these patients underwent complete axillary dissection: two of them (13.33%) had metastatic involvement of other axillary lymph nodes. The other 44 patients didn't receive further surgical axillary procedure. No axillary recurrences in these patients were found during a median follow up of 65.3±9.65 months (range 42-78 months). CONCLUSION: Based on the results and according to some recent randomized trials we can say that axillary lynphadenectomy can be avoided when micrometastases are found in sentinel lynph nodes. It should be performed anyway, depending on the analysis of the biomedical profile of the tumor. KEY WORDS: Breast carcinoma, Micrometases, Sentinel lymph node.