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Chemotherapeutic evaluation using clinical criteria in spontaneous, autochthonous murine breast tumors
R L Stolfi1, L M Stolfi, R C Sawyer
1Department of Surgery, Catholic Medical Center of Brooklyn, and Queens, Inc., Woodhaven, NY 11421.
Abstract:
Six drugs, three of which are considered to be active against human breast cancer [melphalan (PAM), cyclophosphamide (CTX), and 5-fluorouracil (FUra)] and three of which have failed to demonstrate activity against human breast cancer [N-phosphonacetyl-L-aspartate (PALA), cytarabine (ara-C), and 6-thioguanine (TG)], were tested at optimal weekly doses in (BALB/-cfC3H X DBA/8)F1 (CD8F1) mice bearing spontaneous, autochthonous breast tumors averaging 300 mg. When treatment was evaluated by laboratory criteria (i.e., tumor growth inhibition in comparison to vehicle-treated, size-matched controls), all six of the drugs tested were judged to be active. However, when the criteria for positive drug activity consisted of the attainment of tumor regressions of greater than or equal to 50% in greater than or equal to 20% of the treated individuals (i.e., analogous to clinical criteria), only the three drugs that are known to be active against human breast cancer (PAM, CTX, and FUra) were judged active against the spontaneous murine breast tumors. PALA, ara-C, and TG failed to demonstrate regressing activity against the spontaneous murine breast tumors. With a caveat concerning the limited spectrum of drugs evaluated in this study, it can be concluded that the CD8F1 breast tumor model demonstrated 100% correlation with human breast cancer in terms of both positive and negative drug sensitivity when the criteria for evaluation were parallel.
Insights
This study evaluated six breast cancer drugs in mice. Using clinical criteria, the CD8F1 mouse model accurately predicted human breast cancer drug sensitivity, showing high correlation for both active and inactive drugs.
Area of Science:
- Oncology
- Pharmacology
- Translational Cancer Research
Background:
- Accurate preclinical models are crucial for predicting human cancer drug efficacy.
- The CD8F1 mouse model with spontaneous breast tumors is a potential tool for evaluating breast cancer therapeutics.
Purpose of the Study:
- To assess the predictive value of the CD8F1 mouse breast tumor model for human breast cancer drug sensitivity.
- To compare laboratory criteria versus clinical criteria for evaluating drug activity in this model.
Main Methods:
- Six drugs (3 active, 3 inactive against human breast cancer) were tested in CD8F1 mice with spontaneous tumors.
- Drug activity was evaluated using both tumor growth inhibition (laboratory criteria) and tumor regression rates (clinical criteria).
Main Results:
- Laboratory criteria indicated all six drugs were active.
- Clinical criteria revealed only the three known active drugs (melphalan, cyclophosphamide, 5-fluorouracil) showed significant tumor regression.
- The inactive drugs (PALA, cytarabine, 6-thioguanine) failed to induce tumor regression.
Conclusions:
- The CD8F1 mouse breast tumor model, when evaluated with clinical criteria, demonstrated 100% correlation with human breast cancer drug sensitivity.
- This model shows promise for preclinical evaluation of breast cancer drugs, accurately predicting both positive and negative responses.