San Antonio Breast Cancer Symposium 2015. Dec.8-12

Liquid biopsies (based on analysis from the BOLERO-2 clinical trial) found that D538G and Y537S mutations in the estrogen receptor 1 (ESR1) gene are a prognostic indicator for the advanced ER+ cohort.

http://www.aacr.org/Newsroom/Pages/News-Release-De...

Thank you all for the links! My head is spinning from all the info!

In Diagnostics news: Caris Life Sciences' Non-Invasive Liquid Biopsy Platform ADAPT Biotargeting System Demonstrates Potential to Improve Accuracy of Breast Cancer Diagnosis
Study Shows ADAPT Biotargeting System May be an Effective Diagnostic Adjunct to Routine Mammography for Women with Dense Breast Tissue

Caris Life Sciences presented results from the first study using its technology called ADAPT (Adaptive Dynamic Artificial Poly-ligand Targeting) Biotartgeting System to perform multiplexed biomarker discovery in human plasma. The study shows blood plasma contains circulating complexes which contain information that could serve as a diagnostic adjunct to mammography for women with dense breast tissue. Researchers reported results of experiments indicating that ADAPT is equally effective in difficult cases for which imaging technologies are insufficient for characterizing breast tissue as cancerous or non-cancerous.

Targeting copper to treat breast cancer?
Interesting study of a drug called tetrathiomolybdate (TM) that mops up copper. Presented by Dr. Linda Vahdat of Weill Cornell Medical College.
Article is here.
At a median follow-up of nearly five years, 62 other women in the 75 patient TM trial also had no detectable cancer. Among them were 12 of the 15 other women with stage IV triple negative. Interesting, but many challenges to validate in a Phase 3 trial.

more info:

P3-02-02 Targeting the tumor microenvironment: A phase II study of copper-depletion using tetrathiomolybdate (TM) in patients (pts) with breast cancer (BC) at high risk for recurrence
Nackos E, Willis A, Kornhauser N, Ward M, Andreopoulou E, Cigler T, Moore A, Fitzpatrick V, Cobham M, Schneider S, Wiener A, Guillaume-Abraham J, Warren JD, Rubinchik A, Lane M, Mittal V, Linda V. Weill Cornell Medical College, New York, NY; Weill Cornell, New York Presbyterian Hospital, New York, NY; Cornell University, Ithaca, NY.

Immunotherapy / Vaccine news: "Robust generation of T-cell immunity to HER2 in HER2+ breast cancer patients with a degenerate subdominant HLA-DR epitope vaccine."
TapImmune presents new data showing robust generation of T-Cell Immunity
- Vaccination with TPIV 100 boosts T-cell immunity to HER2 in HER2+ patients
- Provides catalyst to start Phase II studies

For the AH, LCIS, and DCIS camp:
Chemoprevention with Tamoxifen or Anastrozole significantly reduces the risk of invasive breast malignancies in women with Atypical Hyperplasia (AH), LCIS, and DCIS.
The prospective randomized trial NSABP B-24 randomly assigned 364 women with ER+ DCIS to receive Tamoxifen and 368 to receive placebo, and at a median follow-up of 14.5 years found breast cancer-free survival to be superior among women who received Tamoxifen over placebo.

More research on targeting ESR1 mutations. .pdf link not posting properly, so pasting abstract summary.

S3-04. "ESR1 coregulator binding inhibitor (ECBI) as a novel therapeutic to target hormone therapy resistant metastatic breast cancer"
PI: Vadlamudi, Ratna (RK)
The University of Texas Health Science Center at San Antonio

Summary: Despite initial positive response to Endocrine therapies, most patients develop resistance to these drugs and tumors recur as mets. Resistant tumors retain ESR1-expression, acquire mutations and exhibit alterations in the levels and functions of coregulators that contribute to estrogen independent ESR1-signaling. There is a critical need to develop novel therapeutics that target ligand independent interaction of coregulators with ESR1.
AEs/AIs are ineffectual in disrupting ESR1 protein-protein interactions that occur in therapy-resistant and metastatic cells. Towards this end, we have rationally designed a lead small organic molecule (ESR1 coregulator binding inhibitor, ECBI) that can emulate ESR1 coregulator NR box motif in the structural context critical for ESR1 signaling.
Our preliminary results show that ECBI can function as natural tumor suppressor, and block tumor growth in vivo. ECBI can control multiple pathways, presenting the prospect of one ECBIs blocking numerous protein-protein interactions between critical coregulators with ESR1 in breast cancer, thus has potential to prevent development of resistance to these therapies. ECBI have pharmacologic advantages, associated with fewer systemic side effects and has potential to delay initiation of toxic systemic chemotherapy. Funds from this CPRIT-Bridging the Gap proposal will provide therapeutic utility, biomarker and cGMP-manufactured drug product formulation to enable IND filing and set stage for future initiation of Phase I trials. Successful completion of the proposed studies will lead to the development of first-in-class cancer therapy drugs that addresses the critical need of targeting therapy resistance and metastasis of breast cancer and to commercialize novel drugs that are efficacious against ESR1-coregulator driven breast tumors.
* Note: Sounds great. Need to start Phase 1 trials. Sadly, this is years from the clinic. Ugh...

Immunotherapy news for TN cohort:
"Abraxane and immune checkpoint inhibitor show very promising tumor response in TNBC metastatic disease".
Upfront treatment with the PD-L1 inhibitor Atezolizumab (MPDL3280A) plus nab-paclitaxel (Abraxane) showed a confirmed objective response rate (ORR) of 66.7% in patients with metastatic TNBC.

Adjuvant Capecitabine (Brand name: Xeloda) Boosts Survival Rates in HER2-Negative Breast Cancer.

These results come from the Phase III CREATE-X/JBCRG-04 trial, which started in 2007.
This trial originated in Japan, thus didn't appear in clinicaltrials.gov website.
Official title: "A phase III trial of adjuvant capecitabine (Xeloda) with HER2-negative pathologic residual invasive disease after neoadjuvant chemo."

After standard neoadjuvant chemo containing an Anthracycline and/or Taxane, postoperative adjuvant use of Capecitabine improved disease-free survival (DFS). Overall survival (OS) was significantly improved by Capecitabine adjuvant therapy for non-pCR or node-positive patients after neoadjuvant chemo."
A combination of capecitabine and adjuvant therapy dropped the risk of recurrence by 30% and prolonged survival by 40% for patients with residual breast cancer post-neoadjuvant chemotherapy and surgery, according to phase III data.

"yay! John!!"

Ditto!!

Immunotherapy news using cyclophosphamide with Aromasin:

[P2-11-11] Phase II trial of Exemestane (Aromasin) with immunomodulatory oral cyclophosphamide in metastatic hormone receptor (HR)-positive breast cancer: Prolonged progression-free survival (PFS) in patients with distinct T regulatory cell (Treg) profile

Background: Resistance to endocrine therapies in HR+ is a significant challenge. The AI Exemestane (EXE) has demonstrated short-term efficacy in metastatic HR+ HER2- (mHR+BC) that has progressed during treatment with a non-steroidal AI. Combination strategies have not shown a survival benefit. Immunotherapy represents a promising approach as it may increase durability of responses. Low dose cyclophosphamide (CTX) has demonstrated efficacy in combination with neoadjuvant Letrozole in HR+, conceivably by enhancing anti-tumor immune responses. Here we investigated whether EXE combined with immunomodulatory CTX could provide durable responses in heavily pretreated patients and assessed immunological profiles (NCT01963481).

Conclusion: EXE and CTX had a favorable safety profile with evidence of clinical activity in patients with heavily pretreated mHR+BC, including durable responses in liver and bone. Correlative studies are ongoing to identify potential biomarkers of response or resistance to therapy.