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Navigating the evolving treatment landscape in mTNBC: What are the key considerations for clinical practice today?

  • Downloads including slides are available for this activity in the Toolkit
Learning Objectives

After watching this activity, participants should be better able to:

  • Evaluate clinical evidence for the use of immune checkpoint inhibitors (ICIs) in PD-L1-positive mTNBC in the first-line setting and its applicability to clinical practice
  • Translate the latest clinical evidence for approved and emerging antibody–drug conjugates (ADCs) for patients with mTNBC into current and future clinical practice
  • Outline the potential for targeted therapy with poly (ADP-ribose) polymerase (PARP) inhibitors in the BRCA-mutated TNBC treatment landscape

In this activity, Prof. Peter Schmid, a breast cancer specialist, and Dr Marleen Kok, a medical oncologist, discuss the evolving treatment landscape in the management of metastatic triple negative breast cancer (mTNBC). They consider the mechanisms of action, the current clinical efficacy evidence for immune checkpoint inhibitors (ICIs), antibody–drug conjugates (ADCs) and poly (ADP-ribose) polymerase (PARP) inhibitors, and how to personalize treatment. The discussion is guided by pre-canvassed questions provided by the breast cancer clinical community.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

This activity has been designed to meet the educational needs of oncologists, including breast cancer specialists involved in the management of triple negative breast cancer.


USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant financial relationships are listed below. All individuals not listed have no relevant financial relationships.


Prof. Peter Schmid discloses: Advisory board or panel fees from AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Eisai, Merck, Novartis, Pfizer, Puma Biotechnology and Roche. Grant/research support from Astellas, AstraZeneca, Genentech, Novartis, OncoGenex, Roche and Medivation.

Dr Marleen Kok discloses: Advisory board or panel fees from AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Merck Sharp & Dohme, and Roche. Speaker’s bureau from Gilead Sciences; Bristol Myers Squibb and Roche (relationships terminated).

Content reviewer

Kaitlin Hendrix, MSN, APRN, AOCNP has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Directors

Holly Gilbert-Jones and Kathy Day have no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact



This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (

Advanced Practice Providers

Physician Assistants may claim a maximum of 1.0 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 29 September 2022. Date credits expire: 29 September 2023.

If you have any questions regarding credit please contact

This activity is CE/CME accredited

To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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  • Downloads including slides are available for this activity in the Toolkit

Topics covered in this activity

Breast Cancer
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Navigating the evolving treatment landscape in mTNBC: What are the key considerations for clinical practice today?
1.0 CE/CME credit

Question 1/5
A 55-year-old woman presents with primary disease and a disease-free interval of 8 months. She is negative for the BRCA1 and BRCA2 genes, but a breast-tissue biopsy reported a PD-L1 CPS >10. What would your preferred treatment option be?

CPS, combined positive score; PD-L1, programmed death-ligand 1.

The IMpassion130 trial investigated atezolizumab in patients with a disease-free interval of ≥12 months,1 whereas the KEYNOTE-355 trial investigated pembrolizumab and included patients with a disease-free interval of ≥6 months.2 The KEYNOTE-355 study also reported results based on PD-L1 CPS ≥1 and ≥10. While both trials showed a benefit with checkpoint inhibitors over comparator chemotherapy,1,2 this patient more closely matches the KEYNOTE-355 eligibility criteria, making pembrolizumab the more suitable choice.


CPS, combined positive score; PD-L1, programmed death-ligand 1.


  1. Schmid P, et al. N Engl J Med. 2018;379:2108–21.
  2. Cortés J, et al. Lancet. 2020;396:1817–28.
Question 2/5
Your patient presents with active metastatic TNBC without brain metastases that has relapsed after two prior lines of chemotherapy. She has asked to be considered for treatment with sacituzumab govitecan. What advice would you give regarding her treatment options?

ADC, antibody–drug conjugate; TNBC, triple-negative breast cancer.

Results from the ASCENT trial showed that in patients who had received at least two prior lines of chemotherapy, the ADC sacituzumab govitecan significantly improved PFS versus chemotherapy (5.6 months vs 1.7 months, respectively; HR 0.41, 95% CI 0.32–0.52; p<0.001) and OS (12.1 months vs 6.7 months, respectively; HR 0.48, 95% CI 0.38–0.59; p<0.001).


ADC, antibody–drug conjugate; CI, confidence interval; HR, hazard ratio; OS, overall survival; PFS, progression-free survival.


Bardia A, et al. N Engl J Med. 2021;384:1529–41.

Question 3/5
How can trial data support the use of HER2 status to guide treatment decisions for ADC therapy such as trastuzumab deruxtecan in TNBC?

ADC, antibody–drug conjugate; HER2, human epidermal growth factor receptor 2; PFS, progression free survival; OS, overall survival; TNBC, triple negative breast cancer.

Patients who express HER2 but at levels too low to be classified as HER2 positive (i.e. HER2-low) account for over 20% of patients with TNBC.1 Results from the DESTINY-Breast04 trial demonstrated prolonged PFS in patients with TNBC (8.5 months vs 2.9 months; HR 0.46, 95% CI 0.24–0.89) and OS (18.2 months vs 8.3 months; HR 0.48, 95% CI 0.24–0.95) treated with trastuzumab deruxtecan versus chemotherapy, respectively.2


CI, confidence interval; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; PFS, progression free survival; OS, overall survival; TNBC, triple negative breast cancer.


  1. Gampenrieder SP, et al. Breast Cancer Res. 2021;23:112.
  2.  Modi S, et al. N Engl J Med. 2022;387:9–20.
Question 4/5
How do PARP inhibitors trigger apoptosis in patients with a germline BRCA1/2 mutation?

PARP, poly(ADP-ribose) polymerase.

PARP is a family of enzymes that facilitates base excision repair following DNA single-strand breaks. PARP inhibition means single-strand breaks in DNA accumulate, which eventually results in double-strand breaks. In cells with BRCA1 or BRCA2 mutations, homologous recombination is disrupted and double-strand breaks cannot be repaired, which leads to apoptosis.


PARP, poly(ADP-ribose) polymerase.


Barchiesi G, et al. Front Oncol. 2021;11:769280.

Question 5/5
In patients initiated on PARP inhibitor therapy, which of the following side effects can impair quality of life if not appropriately managed?

GI, gastrointestinal; PARP, poly(ADP-ribose) polymerase.

Nausea and GI toxicities are commonly reported in patients treated with PARP inhibitors, along with anaemia.1,2 Supportive treatments and dose interruptions can help manage treatment toxicities, allowing patients to remain on the treatment regimen.3


GI, gastrointestinal; PARP, poly(ADP-ribose) polymerase.


  1. Robson M, et al. N Engl J Med. 2017;377:523–33.
  2. Robson M, et al. Ann Oncol. 2019;30:558–66.
  3. Cortesi L, et al. Target Oncol. 2021;16:255–82.
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