[GS4-01] Results from CONTESSA: A phase 3 study of tesetaxel plus a reduced dose of capecitabine versus capecitabine alone in patients with HER2-, hormone receptor + (HR+) metastatic breast cancer (MBC) who have previously received a taxane

O'Shaughnessy J, Schwartzberg L, Piccart M, et al.

The authors conclude that: An all-oral regimen of tesetaxel plus a reduced dose of capecitabine significantly improved PFS versus capecitabine alone. Neutropenia was the most frequent Grade ≥3 TEAE. Rates of clinically significant alopecia and neuropathy were low.

Connolly RM, Zhao F, Miller KD, et al.

The authors conclude that: The combination of exemestane and entinostat did not improve survival in AI resistant advanced HR-positive, HER2-negative breast cancer. Pharmacodynamic analysis confirmed target inhibition in entinostat-treated patients.

[GS4-03] Neoadjuvant nab-paclitaxel weekly versus dose-dense paclitaxel followed by dose-dense EC in high risk HR+/HER2- early BC by: results from the neoadjuvant part of ADAPT HR+/HER2- trial

Kuemmel S, Gluz O, Nitz U, et al.

The authors conclude that: Use of neoadjuvant nab-paclitaxel instead of solvent-based paclitaxel appears promising within a short (16-weeks) dose-dense chemotherapy schedule in high-risk HR+/HER2- BC. For the first time, data from a large neoadjuvant randomized trial confirm RS could help to select patients for neoadjuvant chemotherapy in high-risk HR+/HER2- breast cancer (BC).

Harbeck N, Gluz O, Kuemmel S, et al.

The authors conclude that In pN0-1 luminal EBC pts receiving ET alone, pts with RS12-25/ET-response had 5y-iDFS well above 90% and very close to RS0-11 pts. Both groups had excellent similar dDFS and OS. Dynamic ET response thus complements RS as a key selection criterion for omission of chemotherapy in pN0-1 HR+/HER2- EBC.

[GS4-05] Neoadjuvant chemotherapy (NCT) response in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) resistant to endocrine therapy (ET) in the ALTERNATE trial (Alliance A011106)

Ma CX, Suman V, Leitch AM, et al.

The authors conclude that: In pts with NET-resistant ER+/HER2- BC, salvage NCT is not likely to induce a complete or near complete response. More effective treatments are needed for this high-risk ER+/HER2- pt population.

[GS4-06] Discussant

Lajos Pusztai, MD, PhD
Yale University
New Haven, CT

[GS4-07] Assessing prognosis after neoadjuvant therapy: A comparison between anatomic ypAJCC staging, Residual Cancer Burden Class and Neo-Bioscore

van der Noordaa MEM, Yau C, Shad S, et al.

The authors conclude that: The degree of response to NAC adds important information to pCR versus residual disease. The Neo-Bioscore was not prognostic among patients with pCR, suggesting that clinical stage (including subtype and grade) adds little information in the setting of a pCR. In contrast, both RCB and Neo-Bioscore provide additional prognostic information to the conventional ypAJCC staging among non-pCR patients, suggesting that clinical stage, tumor biology as well as extent of residual disease all contribute to prognosis in the setting of residual disease after NAC.

[GS4-08] Clinical utility of repeated circulating tumor cell (CTC) enumeration as early treatment monitoring tool in metastatic breast cancer (MBC) - a global pooled analysis with individual patient data

Janni W, Yab TC, Hayes DF, et al.

The authors conclude that: 

This large pooled analysis confirms that at a median of 35 days after treatment initiation, follow-up CTC assessments strongly predict overall survival. These results suggest potential clinical utility of CTC monitoring as early response marker in MBC, especially in luminal-like tumors.

Sgroi DC, Treuner K, Zhang Y, et al.

The authors conclude that: Results from this post-hoc analysis of the Trans-aTTom study demonstrated that whereas BCI(H/I) is a significant predictive biomarker of endocrine response, analysis of ER, PR, AR, Ki67 and AR/ER expression showed no interaction with treatment, and lacked the ability to predict benefit of extended tamoxifen in HR+ early stage breast cancer. These results add to the growing body of evidence that BCI (H/I) is distinct in its ability to predict benefit from therapy and interrogates distinct tumor biology that is not captured by other traditional biomarkers.

[GS4-10] Development and validation of a tool integrating the 21-gene recurrence score and clinicopathlogic features to individualize prognosis for distant recurrence and prediction of absolute chemotherapy benefit in early breast cancer

Sparano JA, Crager MR, Tang G, et al.

The authors conclude that: 

We describe a validated clinical tool integrating clinicopathologic and genomic features to guide adjuvant chemotherapy of hormone-receptor positive, HER2-negative, axillary node-negative breast cancer with greater precision than using clinicopathologic or genomic data alone. The individualized CT effect prediction provided by the RS, based on contemporary treatments, contributes substantially to the estimate of absolute CT benefit.

van 't Veer LJ, Cardoso F, Poncet C, et al.

The authors conclude that Patients with a 70-gene G-Low risk tumor have an excellent 8 year outcome in the context of C-Low characteristics when recommended for endocrine therapy only, very close to the outcome in the larger group of all G-Low patients regardless of clinical risk. Stratification of C-Low patients in to G-Low and G-high provides meaningful information. The benefit of ACT in C-Low patients with a 70-gene G-High risk tumor needs further confirmation, especially relevant in younger women.