ABSTRACT
Palbociclib has been shown to be a highly effective therapy in hormone receptor positive metastatic breast cancer when used in combination with letrozole or fulvestrant. Grade 3/4 neutropenia is a common side effect although febrile neutropenia is relatively uncommon. Insufficient data exist to describe the hematological safety of palbociclib in African American women (AAW) known to have a high incidence of benign ethnic neutropenia (BEN). PALOMA 1, 2 and 3, the initial phase II/III studies that led to the U.S. Food and Drug Administration (FDA) approval of palbociclib in metastatic breast cancer, only included participants with baseline absolute neutrophil count (ANC) of 1500/mm3 or higher. African American women (AAW) were underrepresented in the PALOMA trials and this may be partially explained by strict requirements for minimal ANC ≥1500/mm3. The ANC of 1500/mm3 for initiation of treatment in those with BEN has been previously challenged. In this study, we propose to lower the ANC cutoff for enrollment to 1000/mm3. PALINA (NCT02692755) is a phase II, single arm, multicenter clinical trial that will enroll 35 patients. The primary endpoint is to assess the proportion of patients who complete therapy without the development of febrile neutropenia or treatment discontinuation due to neutropenia. The secondary endpoints include number of patients who required dose delays or dose reductions in palbociclib attributed to neutropenia, rate of grade 3/4 neutropenia, clinical benefit rate at 24 weeks, the association between metabolite and exosomal signature with disease response and the association between baseline ANC prior to cancer diagnosis and the Duffy Null polymorphism (SNP rs2814778) with hematological safety. PALINA will provide important information about the hematologic safety of palbociclib in AAW with advanced breast cancer.
ABSTRACT
BACKGROUND: Metaplastic carcinoma of the breast is an extremely rare subtype of breast cancer with an incidence of <1% of all breast neoplasms. Metaplastic carcinoma with chondroid differentiation is the rarest among all histologic subtypes of breast cancer. We report a case of infiltrating ductal carcinoma with metaplastic features of chondroid differentiation. CASE PRESENTATION: A 58-year-old-woman presented to our clinic with a 4-month history of a lump in her right breast. On examination, a firm non-tender mass measuring 2×2 cm was noted in the right upper outer quadrant. It was not attached to the underlying structures. Mammography revealed a dense irregular mass in the axillary tail and a circumscribed nodule in the 6 O'clock periareolar region. This was a new development compared to the patient's most recent screening mammogram performed 2 years and 6 months previously. Ultrasound demonstrated a lobulated solid mass in the axillary tail and a simple cyst in the 6 O'clock periareolar region. Biopsy of the areolar region of the right breast revealed atypical duct hyperplasia. Fine needle aspiration cytology of the right breast axillary tail revealed a poorly differentiated invasive carcinoma consistent with mammary duct origin. On histopathological examination, it was an infiltrating ductal carcinoma with metaplastic features of chondroid differentiation. The tumor was estrogen receptor, progesterone receptor, and HER-2 negative with 0% nuclear staining. Ki-67 index was 52% with strong nuclear staining. The overall ELSTON grade of invasive carcinoma was grade 3. The patient received adjuvant chemotherapy with AC-T (adriamycin, cytoxan, and taxol) and is currently undergoing surveillance for recurrent disease. CONCLUSION: Metaplastic breast cancer is an extremely rare subtype of breast carcinoma. Initial management of localized disease consists of wide excision with clear surgical margins followed by radiation or mastectomy and sentinel lymph node biopsy. Although standard breast chemotherapy regimens such as AC-T are routinely used in metaplastic breast cancer in both adjuvant and metastatic settings, outcomes are significantly inferior to other breast subtypes. Further studies are required to explore targeted treatment to achieve better outcomes in this patient population.
ABSTRACT
BACKGROUND AND AIM: Sarcoidosis is a multi-system granulomatous disease of unknown etiology with significant racial and gender differences in disease severity, incidence, and prevalence. Primarily treated in outpatients, limited information is available on hospital outcomes in patients with sarcoidosis. The National Hospital Discharge Survey (NHDS) was analyzed over a 22-year period to determine trends in hospitalization and the impact of concurrent comorbidities. METHODS: Secondary analysis was done of the NHDS, a national survey of inpatient medical care for short stays in nonfederal facilities. RESULTS: There were a total of 750 million hospitalizations over this 22-year period, with 593,455 (0.08%) hospitalizations with a diagnosis of sarcoidosis. The number of hospitalizations increased from 22,650 in 1979 to 39,964 in 2000, and the age-adjusted rate increased from 108 per 100,000 in 1979 to 146 per 100,000 in 2000. Mean rates of hospitalization were 2.3 times higher for females than males and nine times higher for African-Americans. The mean age of patients increased over this period, particularly for white females. Cardiopulmonary diagnoses were the most frequent concurrent comorbidities. Mortality was low with an overall mortality rate of 2.3%. CONCLUSIONS: Sarcoidosis hospitalizations have increased over this time period. Hospitalization rates are highest among women and African-Americans and are frequently associated with comorbid diseases.