Current and New Novel Combination Treatments for Metastatic Triple-Negative Breast Cancer
Round 1
Reviewer 1 Report
The manuscript by Pauls et al provides an up-to-date review on the current treatment options for metastatic triple negative breast cancer (TNBC), with a focus on immunotherapy, PARP inhibitors and antibody-drug conjugates. Additionally, the emergence of new therapy and new drug combinations for advanced TNBC is discussed. Critical clinical trials supporting the treatment options are discussed in detail with the rationales, caveats and key findings summarized properly and nicely presented in tables. Current treatment regimens for metastatic TNBC are nicely illustrated in the Figure.
Minor comments:
In Section 2.3, it should be better classified why LIV-1 is chosen as a target for TNBC.
Author Response
Dear Current Oncology Editor,
Thank you for reviewing our manuscript entitled "Current and Novel Combination Treatments for Metastatic Triple-Negative Breast Cancer ". The comments are much appreciated. Please see below a response to the comments provided by the reviewers, detailing all changes that were made to the manuscript.
We hope that these changes will improve the manuscript and make it a valuable contribution to your journal. We look forward to your response.
Sincerely,
Dr. Mehrnoosh Pauls, Dr. Stephen Chia & Nathalie LeVasseur
BC Cancer Vancouver Centre, University of British Columbia
600 W 10th Ave
Vancouver, BC V5Z 4E6.
Reviewer(s)' Comments to Author:
Reviewer 1
- In Section 2.3, it should be better classified why LIV-1 is chosen as a target for TNBC.
Author Response:
Thank you for this comment. We have added the paragraph below to the manuscript found at lines 328-247 in order to address this point.
LIV-1 was previously studied in HR positive tumors and subsequently was found to be upregulated in TNBC. Early phase studies have shown promising anti-tumour activity in heavily treated metastatic TNBC. In a phase I trial dose-escalation and expansion cohort, safety and antitumor activity of SGN-LIV1a were evaluated among 44 locally advanced or metastatic TNBC (29). Their results were encouraging, showing ORR of 32%, disease control rate (DCR) of 64% and CBR of 36% among 16 heavily treated advanced TNBC. Median PFS was 11.3 weeks (95% CI 6.1-17.1), with ten patients remaining on treatment (29). These early phases led to openings of other studies investigating SGN-LIV1a as a therapeutic agent among advanced TNBC both as monotherapy and combination therapy.
Author Response File: 
Author Response.docx
Reviewer 2 Report
The work deals with overviewing of TNBC, being of the severe disease among patients nowadays.
Declaring that there are challenges to search and discovery of new pathological agents related to TNBC, the suggested manuscript overviews the up-to-date status as for advances and developments in this scope of investigation.
The manuscript is well prepared and established including recent and the most recent developments and knowledge in discovering novel markers referred to the TNBC. Also, the English is accurate with no need for further improvement.
I especially value an exhaustive Table that includes clinical trials for advanced TNBC.
There are only few remarks from my side:
1. Please, in the subchapter 1.1, follow the upgrade provided:
“Despite advancements in the treatment of HR positive and HER2 positive breast cancers, chemotherapy given as monotherapy or in combination remains the mainstay of treatment for breast cancer [https://doi.org/10.1515/biol-2019-0070]. This also includes the TNBC.”
2. In conclusion, please provide the future aims of the authors in TNBC field of investigation if there are any.
Author Response
Dear Current Oncology Editor,
Thank you for reviewing our manuscript entitled "Current and Novel Combination Treatments for Metastatic Triple-Negative Breast Cancer ". The comments are much appreciated. Please see below a response to the comments provided by the reviewers, detailing all changes that were made to the manuscript.
We hope that these changes will improve the manuscript and make it a valuable contribution to your journal. We look forward to your response.
Sincerely,
Dr. Mehrnoosh Pauls, Dr. Stephen Chia & Nathalie LeVasseur
BC Cancer Vancouver Centre, University of British Columbia
600 W 10th Ave
Vancouver, BC V5Z 4E6.
Reviewer 2
- Please, in the subchapter 1.1, follow the upgrade provided:
Author response:
Thank you for this comment. We have clarified the statement in lines 36-38 to avoid confusion.
Despite the development of targeted agents for the treatment of HR-positive and HER2-positive breast cancers, cytotoxic chemotherapy remains integral to the treatment of breast cancer, particularly triple-negative breast cancer.
- In conclusion, please provide the future aims of the authors in TNBC field of investigation if there are any.
Author response:
Thank you for this comment. We have added the following to the conclusion in lines 435-450 of the revised manuscript.
Moving forward, a greater understanding of tumour biology will undoubtedly continue to move the field beyond chemotherapeutics. As we progress toward personalized cancer treatment, the integration of tumour genomics, transcriptomics, microenvironment and the immune milieu will be at the core of new developments in the treatment of triple-negative breast cancer. Currently, at our centre, there are multiple ongoing clinical trials evaluating novel combinations in patients with advanced TNBC which could transform the therapeutic landscape. Additionally, our group is evaluating the clinical utility of precision medicine by utilizing tumour genomic alterations to inform oncological treatment. A notable example is the ongoing evaluation of liquid genomic testing to detect tier 1 variants of clinical significance among mTNBC that could be used to inform therapeutic approaches or render patients eligible for tumour agnostic clinical trials (PREDiCTI TNBC trial). Another such program is the Personalized Oncogenomics Program (POG) which is utilizing whole-genome and transcriptome analysis to identify potentially informative and actionable molecular alterations, in addition to the evaluation of gene expression signatures and potential predictors of the immune response. Notwithstanding the recent advances in mTNBC, the need for a more refined approach to treatment for these patients remains an unmet need that merits future study.
Author Response File: Author Response.docx
