40486-70

Activity of cisplatin in triple-negative breast cancer in comparison to other cancer types in fresh tumor cell culture assay using a cell death endpoint

Category: 
Detection / Diagnosis
Session Type and Session Title: 
General Poster Session A
Abstract Number: 

61

Citation: 
Author(s): 

L. Weisenthal; Weisenthal Cancer Group, Huntington Beach, CA


Abstract: 

Background: Prognosis of triple negative (ER-/PR-/Her2-) breast cancer (TNBC) is greatly improved by complete response to chemotherapy. The role of cisplatin in breast cancer treatment remains unclear. Methods: We tested cisplatin, doxorubicin, cyclophosphamide (4HC), and docetaxel against three dimensional cell clusters obtained from fresh clinical biopsy specimens of human cancer using a 96 hour, continuous drug exposure assay with a cell death (DISC) endpoint (detailed methods: http://weisenthal.org/w_ovarian_cp.pdf). Results: There was a non-significant trend for TNBC to be more resistant in vitro to doxorubicin and docetaxel than non-TNBC, while the activity of cyclophosphamide was, on average, equal in TNBC vs non-TNBC. Some results for cisplatin are shown in the table. The status of ER and Her2 was significantly associated with the activity of cisplatin (shown below), while the status of PR was not significantly associated (PR data not shown). Overall, the LC50 concentration for cisplatin in TNBC was almost 50% less than that in non-TNBC, and equivalent to that in poorly-differentiated, previously-untreated ovarian cancer. Bloom-Richardson 9/9 breast tumors were significantly more sensitive than BR 4-8/9 tumors and poorly-differentiated ovarian tumors were more sensitive than moderate and well differentiated tumors (data not shown). Conclusions: 1. ER- breast cancer is dramatically more sensitive to cisplatin than is ER+ breast cancer. 2. Her2- breast cancer is slightly more sensitive than is Her2+. 3. ER-/Her2- breast cancer is more sensitive than is ER-/Her2+. 4. Poorly-differentiated breast and ovarian tumors are more sensitive than are moderate and well- differentiated tumors. 5. Non-TNBC subsets are more resistant to cisplatin than are cases of platinum-resistant ovarian cancer. 6. TNBC is equally sensitive to cisplatin as is previously-untreated ovarian cancer and cisplatin is the most active of the four tested drugs in TNBC.

Control Cell Survival Following 96-hour Exposure to Cisplatin (%)

Tumor TypeControl cell
survival after
cisplatin 3.3
ug/ml (95% C.I.)
Control cell
survival after
cisplatin 1.65
ug/ml (95% C.I.)
No. of different
fresh tumor
specimens
tested
P2 (comparison
with entire breast
cancer cisplatin
database, n=650)

Breast, ER+46 (41-51)75 (71-79)79N.S. (3.3 ug/ml)
N.S. (1.65 ug/ml)
Breast, ER-22 (16-28)57 (49-65)44< 0.0001
< 0.0001
Breast, Her2+42 (32-53)76 (70-82)30N.S.
N.S.
Breast, Her2-34 (28-40)64 (59-69)73=0.0009
=0.0006
Breast, ER- Her2 +33 (16-50)71 (58-84)11N.S.
N.S.
Breast, ER- Her2 -17 (12-22)50 (41-59)28<0.0001
<0.0001
Ovarian, Poorly-differentiated,
  Untreated
17 (13-21)44 (38-50)90<0.0001
<0.0001
Ovarian, Poorly-Differentiated,
  Relapsed within 6 months
  of treatment
31 (27-35)65 (60-70)93<0.0001
=0.0008
Ovarian, Poorly-
  Differentiated, Relapsed
  greater than 6 months
21 (16-26)53 (47-59)61<0.0001
<0.0001