Protection Induced by Plasmodium falciparum MSP142 Is Strain-Specific, Antigen and Adjuvant Dependent, and Correlates with Antibody Responses

Vaccination with Plasmodium falciparum MSP142/complete Freund's adjuvant (FA) followed by MSP142/incomplete FA is the only known regimen that protects Aotus nancymaae monkeys against infection by erythrocytic stage malaria parasites. The role of adjuvant is not defined; however complete FA cannot be used in humans. In rodent models, immunity is strain-specific. We vaccinated Aotus monkeys with the FVO or 3D7 alleles of MSP142 expressed in Escherichia coli or with the FVO allele expressed in baculovirus (bv) combined with complete and incomplete FA, Montanide ISA-720 (ISA-720) or AS02A. Challenge with FVO strain P. falciparum showed that suppression of cumulative day 11 parasitemia was strain-specific and could be induced by E. coli expressed MSP142 in combination with FA or ISA-720 but not with AS02A. The coli42-FVO antigen induced a stronger protective effect than the bv42-FVO antigen, and FA induced a stronger protective effect than ISA-720. ELISA antibody (Ab) responses at day of challenge (DOC) were strain-specific and correlated inversely with c-day 11 parasitemia (r = −0.843). ELISA Ab levels at DOC meeting a titer of at least 115,000 ELISA Ab units identified the vaccinees not requiring treatment (noTx) with a true positive rate of 83.3% and false positive rate of 14.3 %. Correlation between functional growth inhibitory Ab levels (GIA) and cumulative day 11 parasitemia was weaker (r = −0.511), and was not as predictive for a response of noTx. The lowest false positive rate for GIA was 30% when requiring a true positive rate of 83.3%. These inhibition results along with those showing that antigen/FA combinations induced a stronger protective immunity than antigen/ISA-720 or antigen/AS02 combinations are consistent with protection as ascribed to MSP1-specific cytophilic antibodies. Development of an effective MSP142 vaccine against erythrocytic stage P. falciparum infection will depend not only on antigen quality, but also upon the selection of an optimal adjuvant component

Breast cancer in women < or = 35 years: review of 1002 cases from a single institution.

BACKGROUND: Early-onset breast cancer may differ with respect to etiology, clinical features and outcome compared with breast cancer in older women. To gain further insight, we retrospectively reviewed the clinical features and outcome of women 2 cm in 61%) and nodal status in 888 (lymph node positive in 52%). Modified radical mastectomy was performed in 568 (57%) and breast-conservation surgery (BCS) in 422 (42%). Five hundred sixteen (51%) patients received adjuvant radiotherapy and five hundred thirty-four (53%) adjuvant systemic therapy. Two hundred ninety-three (29%) patients had a family history of breast cancer (FH). Contralateral breast cancer (CBC) occurred more frequently in women with FH (P range 0.042-0.008). Local recurrence (LR) was 37% and 73% at 10 years in those treated by BCS with and without radiotherapy, respectively. At 10 years, disease-free survival (DFS) was 30% and overall patient survival 48%. CONCLUSIONS: In this cohort, breast cancer was usually self-diagnosed and tumors were > 2 cm at presentation in approximately two-thirds of cases, suggesting the possibilities of a delay in diagnosis, more aggressive tumors or both. Our results are compatible with the known association of breast cancer FH with increased CBC. Our data also corroborates the suggestion that positive genetic testing in this age group should lead to consideration of more aggressive ipsilateral and contralateral breast management. In those receiving adjuvant irradiation after BCS, the LR rate was high, but did not impact on overall survival

Breast cancer in women &lt; or = 35 years: review of 1002 cases from a single institution.

BACKGROUND: Early-onset breast cancer may differ with respect to etiology, clinical features and outcome compared with breast cancer in older women. To gain further insight, we retrospectively reviewed the clinical features and outcome of women &lt; or = 35 years with primary breast cancer seen at our institution over a 30-year period. PATIENTS AND METHODS: Charts were reviewed for women with operable breast cancer diagnosed &lt; or = 35 years of age seen at the Princess Margaret Hospital (PMH), Toronto from 1965-1994. RESULTS: One thousand eighty-six women with non-metastatic invasive breast cancer, aged 18.3-35.6 years (median 32.1 years) were referred to PMH. Symptoms at presentation included: self-detected breast lump (83%), other breast symptom (10%), physician diagnosis (4%) and unknown (3%). Tumor size was known in 936 (&gt;2 cm in 61%) and nodal status in 888 (lymph node positive in 52%). Modified radical mastectomy was performed in 568 (57%) and breast-conservation surgery (BCS) in 422 (42%). Five hundred sixteen (51%) patients received adjuvant radiotherapy and five hundred thirty-four (53%) adjuvant systemic therapy. Two hundred ninety-three (29%) patients had a family history of breast cancer (FH). Contralateral breast cancer (CBC) occurred more frequently in women with FH (P range 0.042-0.008). Local recurrence (LR) was 37% and 73% at 10 years in those treated by BCS with and without radiotherapy, respectively. At 10 years, disease-free survival (DFS) was 30% and overall patient survival 48%. CONCLUSIONS: In this cohort, breast cancer was usually self-diagnosed and tumors were &gt; 2 cm at presentation in approximately two-thirds of cases, suggesting the possibilities of a delay in diagnosis, more aggressive tumors or both. Our results are compatible with the known association of breast cancer FH with increased CBC. Our data also corroborates the suggestion that positive genetic testing in this age group should lead to consideration of more aggressive ipsilateral and contralateral breast management. In those receiving adjuvant irradiation after BCS, the LR rate was high, but did not impact on overall survival