PurposeThe aim of this study was to investigate the breast cancer (BC) molecular subtypes according to its surrogate immunohistochemistry (IHC) markers. We conducted a preliminary study, to correlate the clinical pathological profiles and molecular subtypes of breast cancer in Luanda, Angola.MethodsFrom January 2011 to 30 December 2014, 140 consecutive cases of microscopically confirmed invasive breast carcinoma were classified regarding histology and IHC (ER, PR, HER2, and Ki-67). Surrogate molecular subtypes were classified according to ESMO recommendations.ResultsAll patients were female; the median age was 47 years (24–84 years). Invasive carcinoma NST was the most common type (91.4%) and grade 2 was prevalent (70.7%). Most tumours were locally advanced (stage III – 65% and stage IV – 3.6%). In 140 studied cases, 74 (52.8%) malignancies were hormone receptor positive; 25.7% were luminal A like, 19.3% luminal B and HER2 negative like, 7.9% luminal B and HER2-positive like, 15.7% HER2 positive, and 31.4% were triple negative.ConclusionWomen’s BC in Luanda-Angola is diagnosed at a young age and at an advanced stage. The two predominant molecular subtypes are HR positive and triple negative. The percentage of HER2-positive BC cases was high. Determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angolan women with BC. There is an urgent need to study a prospective BC series in order to confirm the present results.
The main complain of patients with partial androgen insensitivity patients (PAIS) is undervirilization signs and the small penile length. Supplemental androgen therapy has enhanced virilization in only a few patients with PAIS. Aromatase inhibitors as anastrozole and letrozole are nonsteroidal inhibitors able to bind reversibly to the heme group of cytochrome P450 reducing estrogen and estrone levels and increasing LH and FSH levels and consequently testosterone levels. We hypothesized that the combination of high-dose testosterone with anastrozole can maintain a sustained elevated testosterone levels and also deviated testosterone metabolization from estrogen to DHT, therefore increasing penile length.
Case Report
This experimental treatment was proposed and both patient and parents willing to participate. Patient was firstly evaluated at 7 yrs of age. The hemizygous c.2599G>C; p.V867L
AR
in the ligand-binding domain (LBD) was found in both affected siblings. He was previously submitted to three unsuccessful genital masculinizing surgeries and bilateral orchidopexia. The external genitalia presented a microphalus (penile length of 2 cm, -4.5 SDS), perineal hypospadias and bilateral topic testis. He received testosterone cypionate (50 mg IM injections monthly, for 3 times at age of 7 and 200 mg IM injections monthly, for 4 times at age of 8); topic DHT gel (5-10 g/daily for three months at age of 7 yrs). At age of 12.3 yrs, the genital masculinization surgeries were completed, penile length was 3.5 cm (-2.6 SDS), testicular size of 2.6x1.5 cm and pubic hair Tanner II stage. LH and FSH levels were (9.4 and 3.2 IU/L respectively), testosterone (304 ng/dL), DHT (26 ng/dL) and estradiol (<17 pg/mL). The effect of 200 mg of testosterone cypionate weekly associated to 1 mg of anastrozole daily was evaluated. After 6 months of treatment, he presented enlargement of penile length (7.0 cm, -1 SDS), and testicular size (3.0x2.0 cm) and Tanner IV of pubic hair. Gynecomastia was absent. The hormonal profile showed: decreased values of LH and FSH (0.8 and 1.1 IU/L respectively), and estradiol (<17 pg/mL) levels, and increased testosterone and DHT levels (1753 and 167 ng/dL, respectively). Bone age did not advance during treatment.
Conclusion
This is the first documentation of successful virilization in a PAIS boy with androgen insensitivity due to a hemizygous missense mutation in
AR
with a combination of high-dose testosterone and aromatase inhibitor.
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