Decrease in Tumorigenic Breast Cancer Cells with Neoadjuvant Lapatinib

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Decrease in Tumorigenic Breast Cancer Cellswith
Neoadjuvant Lapatinib
Angel A. Rodriguez, M.D. Instructor, Lester and
Sue Smith Breast Center Baylor College of Medicine
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Breast Cancer Stem Cells

• Tumorigenic cancer cell or Cancer stem cell
• Self-renewing
• Gives rise to all types of breast cancer
• Able to regenerate a new tumor upon
  transplantation

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Omnis cellula e cellula

• Rudolf Ludwig Karl Virchow (1821-1902) gave a
  celebrated series of 20 lectures in Berlin in
  1858
• He proposed his theory that diseases came from
  abnormal changes within cells.
• Virchow RLK Die Cellularpathologie in ihrer
  Begründung auf physiologische und pathologische
  Gewebenlehre. Berlin Hirschwald, 1858

Adapted from http//library.utmem.edu/exhibits/sta
mps/StampsLarge/VirchowGermany.gif
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Tumorigenic Breast Cancer Cell (TBCs) Hypothesis
Standard Rx TBCs Inhibitor Combination
Complete Response
Tumorigenic Breast Cancer Cells (TBCs) Daughter
Cells
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Relationship between TBCs and Therapy

• Do conventional therapies affect TBCs?
• Chemotherapy
• Endocrine Rx
• 2. Are there specific inhibitors that affect
  self-renewal pathways in TBCs?

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Preoperative Lapatinib Phase II Study
Pathologic assessment
Tumor Size Baseline
Tumor Size Week 6
Lapatinib 6 weeks
Standard trastuzumab/docetaxel 12 weeks
Bx Wk 6
Bx Initial
Surgery
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Clinical Efficacy of Single Agent Lapatinib
(N45)

• Large initial primary cancers
• T size median 10 cm (range 2.5, 30)
• 12 patients (27) had inflammatory br ca
• After 6 weeks of Lapatinib
• Median decrease 50 (0, -100, p0.001)
• CR 7 (3/42)
• PR 69 (29/42)
• SD 21 (9/42)
• PD 2 (1/42)
• 2 patients lost to follow up, 1 still on
  lapatinib

76 (32/42)
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Before And After 6 Weeks Of HER1/2 Blockade With
Lapatinib
BEFORE AFTER
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Before And After 6 Weeks Of Lapatinib
A.
B.
Week 6
Initial
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Changes in TBCs Chemotherapy vs Lapatinib
Chemo (N35)
Lapatinib (N30)
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Changes in mammosphere formation Chemotherapy vs
Lapatinib
Chemo
Lapatinib
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Patient Outcomes

• Chemo Lapatinib?TH
• T size 6.7 cm (3, 13) 10 cm (2.5, 30)
• Palpable nodes 7 (23) 7 (26)
• ER
• positive 15 (48) 7 (26)
• negative 16 (52) 20 (74)
• PgR
• positive 12 (39) 5 (19)
• negative 19 (61) 22 (81)
• Pathologic response
• pCR 2 (7) 11 (41)
• npCR 5 (16) 6 (23)
• PR 24 (77) 10 (37)

7(23)
17(64)
3 patients chose not to receive TH prior to
surgery(all PR), 9 on preoperative treatment, 4
did not have surgery(stageIV), 2 lost to follow
up or dropped out
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Conclusions

• Small subpopulation of cells with tumorigenic
  potential is intrinsically resistant to
  conventional chemotherapy
• The dual kinase inhibitor, lapatinib, may affect
  self-renewal of these TBCs and sensitize them to
  subsequent chemotherapy.
• Specific inhibitors to pathways active in Breast
  Cancer Stem Cells may enhance efficacy of
  current therapies.