Understanding Pembrolizumab: A New Immunotherapy for High-Risk Early-Stage Triple-Negative Breast Cancer

Table of Contents

• Key Points
• Background: Why Triple-Negative Breast Cancer Is Different
• The Biology of TNBC: Subtypes and Genetic Features
• The Treatment Challenge in Early-Stage TNBC
• How Immune Checkpoint Inhibitors Reached Early-Stage Treatment
• Key Neoadjuvant Immunotherapy Trials: The Numbers
• The Landmark KEYNOTE-522 Trial: Design and Dosing
• KEYNOTE-522 Results: What the Numbers Show
• Side Effects and Immune-Related Toxicity
• Biomarkers: Who Benefits Most From Immunotherapy?
• Ongoing Clinical Trials and Future Directions
• Clinical Implications: What This Means for Patients
• Limitations and Open Questions
• Practical Recommendations for Patients
• Frequently Asked Questions
• Source Information

Key Points

• In the KEYNOTE-522 trial of 1,174 patients, adding pembrolizumab to chemotherapy raised the pathologic complete response rate from 51.2% to 64.8% in high-risk, early-stage triple-negative breast cancer.
• The same trial showed 3-year event-free survival of 84.5% with pembrolizumab versus 76.8% with placebo, and distant recurrence occurred in 7.7% versus 13.1%.
• In KEYNOTE-522, benefit was seen across PD-L1 subgroups, unlike metastatic disease where PD-L1 status determines eligibility.
• Grade 3 or higher immune-related side effects occurred in 14.9% of pembrolizumab-treated patients versus 2.1% with placebo, and 27.7% discontinued at least one therapy.
• Overall survival data remain immature, and better biomarkers to predict who benefits most from immunotherapy are still needed.

Background: Why Triple-Negative Breast Cancer Is Different

Triple-negative breast cancer (TNBC) makes up roughly 15% to 20% of all breast cancers. Doctors define it by what the tumor lacks: it does not express the estrogen receptor (ER), does not express the progesterone receptor (PR), and does not overexpress the HER2 protein.

That absence matters. Because TNBC lacks these three targets, it does not respond to the hormone-blocking drugs or HER2-directed therapies that transformed outcomes for other breast cancer types. And TNBC behaves differently in who it affects — it disproportionately strikes younger women and women of color compared to other breast cancer subtypes.

This disease is also biologically aggressive. TNBC has a higher tendency toward early recurrence, and it often spreads to internal organs (visceral involvement) rather than only to bone. Relapse rates have fallen with modern treatments, but the outlook remains unfavorable compared to other subtypes — largely because well-defined molecular targets have only recently begun to be identified.

The good news: substantial research is now underway to find biomarkers (measurable biological signals) that predict relapse. Research is also underway to develop more effective treatments before and after surgery to improve long-term outcomes.

The Biology of TNBC: Subtypes and Genetic Features

TNBC was historically treated as a single disease. Modern molecular analysis shows it is actually a complex and biologically heterogeneous condition — meaning it varies widely from patient to patient at the genetic level.

Gene expression profiling has identified five distinct intrinsic molecular subtypes of breast cancer. More than 90% of basal-like tumors are TNBCs, and TNBCs are enriched for TP53 mutations. A research team led by Lehmann later described six unique molecular signatures of TNBC:

• Basal-like 1
• Basal-like 2
• Mesenchymal
• Mesenchymal-stem-like
• Immunomodulatory
• Luminal androgen receptor

Each of these signatures responds differently to chemotherapy — and more recently, to immunotherapy. Additional classification efforts have reported overlapping findings.

Several other key genetic features appear in TNBC. Roughly 20% of unselected TNBC patients carry defects in BRCA1 or BRCA2 (either inherited/germline or acquired/somatic mutations). These defects impair homologous recombination, a critical DNA repair mechanism, which can make tumors vulnerable to a class of drugs called PARP inhibitors.

Other commonly disrupted signaling pathways in TNBC include RAS/RAF/MEK, PI3K/AKT/mTOR, and JAK/STAT3. These alterations are not clearly established as cancer-driving events in TNBC, but early research suggests multi-kinase inhibition may be a promising strategy.

Molecular subtyping has deepened our understanding of TNBC biology. However, these advances have not yet entered routine clinical care to guide treatment decisions for early-stage patients — a key gap the field is working to close.

The Treatment Challenge in Early-Stage TNBC

For patients with high-risk, early-stage TNBC, chemotherapy given before surgery (neoadjuvant) with anthracyclines and taxanes has remained the backbone of treatment for years — and has barely changed.

TNBC presents a paradox. Patients with early-stage disease tend to achieve higher responses to neoadjuvant chemotherapy than other subtypes, yet they also face a higher risk of early recurrence. Several treatment questions remain unsettled:

• Whether adding platinum-based drugs (like carboplatin) improves long-term outcomes
• What role adjuvant (post-surgery) treatments play beyond capecitabine

The critical problem is this: patients who still have residual (leftover) disease after standard neoadjuvant therapy face a 30% to 40% risk of recurrence and a poor prognosis. New therapeutic approaches are urgently needed.

The approval of pembrolizumab plus chemotherapy greatly expands the available treatment options and offers a real opportunity to improve cure rates for this population.

How Immune Checkpoint Inhibitors Reached Early-Stage Treatment

Progress in the advanced (metastatic) setting paved the road to early-stage treatment. In advanced TNBC, several new strategies gained approval, including PARP inhibitors for tumors with germline BRCA1/2 mutations, the antibody-drug conjugate (ADC) sacituzumab govitecan, and immune checkpoint inhibitor combinations.

In March 2019, atezolizumab plus nab-paclitaxel became the first checkpoint inhibitor to receive accelerated FDA approval for PD-L1–positive advanced TNBC, based on the Phase III IMpassion130 trial. (PD-L1 status was measured with the VENTANA SP-142 companion diagnostic test.)

That approval was conditional on the results of a follow-up trial called IMpassion131. That trial tested atezolizumab plus paclitaxel against paclitaxel alone in a similar patient group and failed to show improved progression-free survival (time before the cancer worsened) with atezolizumab. After review, the FDA no longer supported accelerated approval, and the manufacturer voluntarily withdrew the indication in the United States.

Meanwhile, in November 2020, the FDA approved pembrolizumab combined with taxane or platinum chemotherapy for PD-L1–positive advanced TNBC (defined as a combined positive score, or CPS, of 10 or higher on the DAKO 22C3 test), based on the Phase III KEYNOTE-355 study.

Key Neoadjuvant Immunotherapy Trials: The Numbers

These advances in the metastatic setting led researchers to test immune checkpoint inhibitors in early-stage disease. Results varied across trials — and the differences are instructive.

IMpassion031 (Phase III) tested atezolizumab every 2 weeks plus anthracycline-cyclophosphamide and taxane-based chemotherapy. It improved the pathologic complete response (pCR) rate — the absence of detectable cancer cells in breast tissue and lymph nodes at surgery — to 58% (95% confidence interval [CI], 50 to 65) with atezolizumab versus 41% (95% CI, 34 to 49) with placebo in the intention-to-treat population (a difference of 17%, 95% CI, 6 to 27; one-sided p=0.0044, with a significance boundary of 0.0184).

NeoTRIPaPDL1 (Phase II) took a different approach: neoadjuvant carboplatin plus nab-paclitaxel with or without atezolizumab, followed by surgery and adjuvant anthracycline-based treatment. It did not improve pCR in the intention-to-treat analysis — 48.6% with atezolizumab versus 44.4% without (odds ratio 1.18; 95% CI, 0.74 to 1.89; p=0.48).

TONIC (Phase II) tested different immune-priming strategies in metastatic TNBC. Giving anthracycline chemotherapy before nivolumab produced the highest response rate to immunotherapy — an objective response rate of 35% — compared to other strategies. Collectively, these data suggest that anthracyclines may serve as key chemotherapy agents to prime the immune system.

In the Phase II GeparNuevo trial, 117 patients received an initial 2-week "window" of single-agent durvalumab before neoadjuvant chemotherapy. Those who received this immune-priming window had a more pronounced improvement in pCR than those who received combination therapy alone: 61.0% with durvalumab versus 41.4% with placebo (odds ratio 2.22, 95% CI, 1.06 to 4.64, p=0.035).

Early pembrolizumab trials showed manageable toxicity and improved anti-tumor activity. In the randomized I-SPY 2 trial, pembrolizumab plus neoadjuvant chemotherapy roughly doubled pCR rates (60.0% with pembrolizumab versus 22.0% with placebo) and shifted the distribution of residual cancer burden toward lower disease burden. The Phase Ib KEYNOTE-173 trial, which used a pembrolizumab "run-in" for cycle 1 followed by taxane with or without carboplatin, then doxorubicin and cyclophosphamide (AC), showed promising anti-tumor activity (60.0% pCR, range 49–71%) and a manageable safety profile.

These trials established the basis for the FDA's Breakthrough Therapy designation for pembrolizumab — and ultimately for the pivotal KEYNOTE-522 trial.

The Landmark KEYNOTE-522 Trial: Design and Dosing

KEYNOTE-522 was the first randomized, double-blind, placebo-controlled study of pembrolizumab in early-stage TNBC, testing it in both the neoadjuvant (before surgery) and adjuvant (after surgery) settings.

Patients were eligible if they had newly diagnosed, high-risk, early-stage TNBC, defined as cT1c, N1-2 or cT2-4, N0-2 staging. Patients were excluded if they had active autoimmune disease requiring systemic treatment within the prior 2 years, a clinically significant other medical condition or immunodeficiency, or a need for immunosuppressive therapy.

How the treatment worked:

1. Neoadjuvant phase 1: Pembrolizumab (200 mg intravenously every 3 weeks) or placebo, combined with carboplatin (weekly or every 3 weeks) plus weekly paclitaxel for 4 cycles.
2. Neoadjuvant phase 2: Anthracycline (doxorubicin or epirubicin) plus cyclophosphamide every 3 weeks for 4 cycles.
3. Surgery: Definitive surgery.
4. Radiation: Given if clinically indicated.
5. Adjuvant phase: Pembrolizumab or placebo to complete a full year of treatment. If radiation was needed, adjuvant pembrolizumab or placebo began either alongside radiation or at least 2 weeks after it. Adjuvant capecitabine was not permitted.

A total of 1,174 patients were randomized in a 2:1 fashion to the pembrolizumab or placebo arm. The primary endpoints were pCR (defined as ypT0/Tis ypN0) and event-free survival (EFS) in the intention-to-treat population. Secondary endpoints included safety, overall survival (OS), and pCR in the PD-L1–positive population. PD-L1 expression was tested using the PD-L1 IHC 22C3 pharmDx assay, with a CPS of 1 or higher considered positive.

KEYNOTE-522 Results: What the Numbers Show

The results were substantial and practice-changing. The first interim analysis, among the first 602 patients randomized, showed a pCR rate of 64.8% (95% CI, 59.9 to 69.5) with pembrolizumab-chemotherapy versus 51.2% (95% CI, 44.1 to 58.3) with placebo-chemotherapy — a difference of 13.6% (95% CI, 5.4 to 21.8; p=0.00055).

Importantly, pembrolizumab-chemotherapy increased pCR rates across all subgroups regardless of PD-L1 status. This differs from the metastatic setting, where PD-L1 status predicts pembrolizumab benefit.

• PD-L1–positive patients: pCR 68.9% with pembrolizumab-chemotherapy versus 54.9% with placebo-chemotherapy.
• PD-L1–negative patients: pCR 45.3% with pembrolizumab-chemotherapy versus 30.3% with placebo-chemotherapy.

The 3-year event-free survival rate was 84.5% with pembrolizumab-chemotherapy versus 76.8% with placebo-chemotherapy — a 7.7% absolute improvement. In the pembrolizumab group, 15.7% of patients (123 of 784) experienced any disease-related event or death, compared to 23.8% (93 of 390) in the placebo group (hazard ratio 0.63, 95% CI, 0.48 to 0.82, p=0.00031).

Distant recurrence (cancer spreading to distant organs) occurred in 7.7% (60 of 784) of the pembrolizumab group versus 13.1% (51 of 390) of the placebo group — roughly a halving of distant spread.

Outcomes split sharply by whether patients achieved pCR:

• Patients who achieved pCR: 94.4% EFS with the pembrolizumab regimen versus 92.5% with placebo.
• Patients with residual disease after neoadjuvant therapy: 67.4% EFS with pembrolizumab versus 56.8% with placebo.

This suggests that adjuvant pembrolizumab is potentially most critical in the non-pCR setting — that is, for patients who still have disease left at surgery.

By PD-L1 status, EFS events occurred as follows:

• PD-L1–positive: 14.9% with pembrolizumab versus 21.5% with placebo (hazard ratio 0.67, 95% CI, 0.49 to 0.92).
• PD-L1–negative: 19.5% with pembrolizumab versus 36.2% with placebo (hazard ratio 0.48, 95% CI, 0.28 to 0.85).

There was a trend toward improved overall survival with pembrolizumab (89.7% versus 86.9%), although these data remain immature (meaning not yet enough events have occurred for a definitive conclusion). Distant progression- or recurrence-free survival was 87.0% with pembrolizumab versus 80.7% with placebo.

Based on these findings, on July 26, 2021, the FDA approved pembrolizumab for the treatment of patients with high-risk, early-stage TNBC.

Side Effects and Immune-Related Toxicity

The improved efficacy came with added toxicity, and understanding this is essential. Treatment-related adverse events (TRAEs) of grade 3 or higher across all treatment phases occurred in 77.1% of the pembrolizumab-chemotherapy group versus 73.3% of the placebo-chemotherapy group. Deaths occurred in 0.5% (4 patients) treated with pembrolizumab and 0.3% (1 patient) treated with placebo. The deaths in the pembrolizumab group were attributed to sepsis (a severe whole-body infection) and pneumonitis (lung inflammation). The deaths were also attributed to pulmonary embolism (a blood clot in the lungs) and autoimmune encephalitis (immune attack on the brain).

Most TRAEs and events of interest occurred during the neoadjuvant phase, were low grade, and were largely attributed to chemotherapy. Adverse events of interest occurred in 38.9% of pembrolizumab-treated patients and 18.3% of placebo-treated patients.

Adverse events of interest that were grade 3 or higher occurred in 12.9% of pembrolizumab-treated patients versus 1.8% of placebo-treated patients. The most common severe events in the pembrolizumab group were:

• Severe skin reactions: 3.8%
• Infusion reactions: 2.6%
• Adrenal insufficiency (when the adrenal glands do not make enough hormones): 1.3%

TRAEs that led to discontinuing any therapy occurred in 27.7% of the pembrolizumab group versus 14.1% of the placebo group. Immune-related adverse events (irAEs — side effects caused by the immune system attacking healthy tissue) of grade 3–5 occurred in 14.9% of pembrolizumab-treated patients versus 2.1% of placebo-treated patients. These immune-related adverse events led to treatment discontinuation in 10.9% versus 2.6%, respectively. In the adjuvant setting alone, grade 3–5 irAEs occurred in 2.9% versus 0.3% of patients.

The bottom line for patients: adding carboplatin in the neoadjuvant phase and pembrolizumab in both phases means improved efficacy must be weighed against added toxicity. Comprehensive patient education about irAEs is an essential part of clinical care, and rare, potentially long-lasting immune side effects will need close monitoring going forward.

Biomarkers: Who Benefits Most From Immunotherapy?

TNBC is considered to have the highest immunogenic potential of all breast cancers. It is enriched for BRCA germline mutations and higher somatic mutational load (more genetic errors in the tumor). It is also enriched for more tumor-associated neoantigens (abnormal proteins that the immune system can recognize) — though it is rarely associated with microsatellite instability.

Early- and advanced-stage breast cancers differ in their tumor and immune cell microenvironments, which may affect how well immunotherapy works. The predictive value of standard immune biomarkers also differs by disease stage.

In preclinical (laboratory) studies, high levels of tumor-specific CD8+ T cells (a type of cancer-killing immune cell) soon after neoadjuvant immunotherapy exposure predicted long-term survival. Adjuvant immunotherapy produced lower tumor-specific CD8+ T cells compared to neoadjuvant treatment in mice with intact tumors.

PD-L1 mRNA expression is higher in TNBC and is associated with improved clinical outcomes. In metastatic TNBC, PD-L1 status is an established predictive biomarker of immune checkpoint inhibitor response. But in early-stage TNBC, the benefit of immunotherapy appears to exist independently of PD-L1 expression — even though patients with PD-L1–positive tumors achieved numerically higher pCR rates in KEYNOTE-522. About 80% of patients in each treatment arm of KEYNOTE-522 had PD-L1–positive disease.

Where PD-L1 is expressed — in tumor cells versus immune cells — appears to matter. In GeparNuevo, there was a trend for pCR rates in PD-L1 positive tumors. This trend was significant for PD-L1 expression in tumor cells in the durvalumab arm (p=0.045) and for PD-L1 expression in immune cells in the placebo arm (p=0.040). Tumor mutational burden combined with immune gene expression profile also predicted pCR in that study.

Tumor infiltrating lymphocytes (TILs — immune cells that have moved into the tumor) are a promising biomarker for response to neoadjuvant chemotherapy in early-stage TNBC. The presence of stromal TILs (sTILs — immune cells in the tissue surrounding the tumor) is prognostic and linked to higher pCR rates.

• A pooled analysis of 3,771 patients treated with neoadjuvant therapy found that a 10% increase in sTILs was associated with longer disease-free survival in TNBC patients.
• The Phase III BIG 02–98 trial showed that both sTILs and intratumoral TILs (iTILs — immune cells inside the tumor) were highest in highly proliferative tumors. Both sTILs and iTILs were associated with ER and HER2 negativity.
• Increasing lymphocytic infiltration at diagnosis was significantly associated with favorable prognosis in the ER-negative/HER2-negative subgroup, regardless of chemotherapy backbone. This was particularly true in the lymphocyte-predominant breast cancer (LPBC) subgroup, defined by roughly 50–60% TILs in the tumor specimen.
• Higher TIL levels in residual disease after treatment were also associated with improved recurrence-free and overall survival.

Interestingly, the location of TILs may matter. In GeparNuevo, although sTILs were associated with pCR, iTILs on pretreatment biopsy did not seem to predict pCR. This highlights the need for further study of spatial immunophenotyping — mapping where immune cells sit within and around the tumor. Both the pretreatment composition and the changes during therapy may shape which strategies are needed to boost an anti-tumor immune response.

Despite this progress, better biomarkers for immunotherapy response in early-stage TNBC remain a major unmet need. Standardizing how biomarker tests are run and interpreted will be required before any new biomarker enters clinical practice.

Ongoing Clinical Trials and Future Directions

Multiple ongoing trials are testing pembrolizumab and other immune-modulating strategies in early-stage TNBC:

• NeoPACT (Phase II, 121 patients, NCT03639948): Neoadjuvant pembrolizumab with carboplatin and docetaxel; primary outcome is pCR, secondary outcome is recurrence-free survival.
• NCT04427293 (window-of-opportunity, 12 patients): Neoadjuvant lenvatinib plus pembrolizumab for 1 cycle; primary endpoint is evaluating TILs.
• NCT03199040 (Phase I, 18 patients): Adjuvant neoantigen DNA vaccine with or without durvalumab in patients with residual TNBC; primary endpoint is safety.
• NCT04331067 (Phase Ib/II, 50 patients): Neoadjuvant cabiralizumab plus nivolumab with carboplatin plus paclitaxel versus nivolumab plus carboplatin plus paclitaxel; primary endpoints are percentage change in TILs, tumor-associated macrophages (TAMs), and safety.
• BreastVax (Phase Ib/II, 36 patients, NCT04454528): Comparing neoadjuvant radiation followed by pembrolizumab, pembrolizumab followed by radiation, pembrolizumab alone, and upfront surgery; primary endpoint is feasibility.
• NCT02957968 (Phase II, 32 patients): Neoadjuvant pembrolizumab plus decitabine followed by AC followed by paclitaxel; primary endpoint is increase in TILs after pembrolizumab plus decitabine.
• NCT04373031 (Phase II, 30 patients): Neoadjuvant pembrolizumab-based treatment.

Clinical Implications: What This Means for Patients

The FDA approval of pembrolizumab for high-risk, early-stage TNBC immediately changed the longstanding treatment paradigm for this disease. For the first time, patients with this aggressive subtype have an immunotherapy option that improves the chance of eradicating detectable cancer before surgery. This immunotherapy option also reduces the risk of the cancer returning.

The most striking finding for patients is the benefit in the non-pCR setting. Patients who still have residual disease after neoadjuvant therapy had a 67.4% EFS rate with pembrolizumab versus 56.8% with placebo — a difference of more than 10 percentage points. This is precisely the group that historically faced a 30–40% recurrence risk, so the gain is clinically meaningful.

Another key point: the benefit appeared across PD-L1 subgroups. Unlike in metastatic disease, where PD-L1 status determines eligibility, early-stage patients appear to benefit regardless of PD-L1 status. This simplifies decision-making, because patients do not need to wait for a PD-L1 result to consider the regimen.

Limitations and Open Questions

Several questions remain unresolved.

Overall survival data are still immature — the trend favored pembrolizumab (89.7% versus 86.9%), but longer follow-up is needed before firm conclusions can be drawn. The authors note that deeper insight is needed into which patients truly require the added immunotherapy, given the additional toxicity.

Biomarker development remains an area of significant need. PD-L1 alone does not cleanly separate who benefits from who does not in early-stage disease. TIL measurement, spatial immunophenotyping, and tumor mutational burden are all promising but not yet standardized or ready for routine clinical use.

Optimal chemotherapy partnering is also uncertain. The NeoTRIPaPDL1 trial did not show benefit from adding atezolizumab to a platinum-taxane backbone, while IMpassion031 and KEYNOTE-522 did show benefit with anthracycline-containing regimens. This suggests that the chemotherapy backbone — and possibly the sequence of immune priming — matters. Whether the addition of platinum salts translates into improved long-term outcomes has not been fully established.

Finally, questions remain about the role of adjuvant approaches beyond capecitabine, and how to best manage rare, potentially long-lasting immune-related side effects over the long term.

Practical Recommendations for Patients

1. Ask whether you are eligible. The pembrolizumab regimen is approved for high-risk, early-stage TNBC (stages cT1c, N1-2 or cT2-4, N0-2). Discuss your specific staging and risk category with your oncology team.
2. Understand the schedule. The regimen involves pembrolizumab every 3 weeks plus carboplatin and paclitaxel for 4 cycles, then anthracycline plus cyclophosphamide for 4 cycles. The regimen then involves surgery, possible radiation, and then pembrolizumab or placebo to complete a full year of treatment.
3. Report immune symptoms immediately. Because immune-related side effects can involve the skin, lungs, adrenal glands, and other organs, tell your care team right away about new rashes, breathing changes, severe fatigue, or unusual symptoms. Severe skin reactions (3.8%), infusion reactions (2.6%), and adrenal insufficiency (1.3%) were the most common severe immune events.
4. Expect extra monitoring. Roughly 1 in 4 patients (27.7%) discontinued at least one therapy due to side effects, compared to 14.1% on placebo. Discontinuation is a real possibility — but it is manageable with close monitoring.
5. Know that non-pCR does not mean failure. Even patients with residual disease at surgery had meaningfully better outcomes with pembrolizumab, so the adjuvant portion of treatment matters.
6. Ask about clinical trials. Several ongoing studies are testing new combinations and identify which patients benefit most.

Frequently Asked Questions

What does a pathologic complete response (pCR) mean after treatment?

A pathologic complete response means no detectable cancer cells remain in the breast or lymph nodes when tissue is examined at surgery. In the KEYNOTE-522 trial of 1,174 patients, adding pembrolizumab to chemotherapy raised the pCR rate from 51.2% to 64.8% compared with chemotherapy alone.

What side effects should I watch for during pembrolizumab treatment?

Immune-related side effects can affect the skin, lungs, adrenal glands, and other organs. In the KEYNOTE-522 trial, severe skin reactions occurred in 3.8% of pembrolizumab-treated patients, infusion reactions in 2.6%, and adrenal insufficiency in 1.3%. Report new rashes, breathing changes, severe fatigue, or unusual symptoms to your care team right away.

Does it matter if my tumor is PD-L1 positive or negative for this treatment?

In early-stage triple-negative breast cancer, the benefit of adding pembrolizumab appeared across all subgroups regardless of PD-L1 status. This differs from metastatic disease, where PD-L1 status determines eligibility. So you do not need to wait for a PD-L1 result to consider this regimen with your doctor.

What if I still have cancer left at surgery after neoadjuvant treatment?

Having residual disease does not mean treatment failed. In the KEYNOTE-522 trial, patients with residual disease after neoadjuvant therapy had a 3-year event-free survival rate of 67.4% with pembrolizumab versus 56.8% with placebo. The adjuvant portion of treatment matters and may improve outcomes.

How is the pembrolizumab regimen scheduled?

The regimen starts with pembrolizumab every 3 weeks plus carboplatin and paclitaxel for 4 cycles, then anthracycline plus cyclophosphamide for 4 cycles. The regimen then involves surgery, possible radiation, and finally pembrolizumab or placebo to complete a full year of treatment. Your oncology team will guide you through each phase.

When should a patient with high-risk early-stage triple-negative breast cancer seek a second opinion before starting pembrolizumab plus chemotherapy?

A second opinion is reasonable before committing to this regimen, especially to confirm high-risk staging (cT1c, N1-2 or cT2-4, N0-2) and to weigh the added toxicity against benefit. Treatment-related adverse events of grade 3 or higher occurred in 77.1% with pembrolizumab-chemotherapy versus 73.3% with placebo-chemotherapy, and 27.7% discontinued at least one therapy. Because benefit appeared across PD-L1 subgroups, an independent review can help clarify whether the regimen and chemotherapy backbone fit your situation. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Targeted Treatment for High-Risk Early-Stage Triple-Negative Breast Cancer- Spotlight on Pembrolizumab

Authors: Nusayba A. Bagegni, Andrew A. Davis, Katherine K. Clifton, Foluso O. Ademuyiwa

Author affiliation: Division of Oncology, Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, 63110, USA

Publication: Breast Cancer: Targets and Therapy, 2022;14:113–123. Published April 29, 2022. DOI: 10.2147/BCTT.S293597. Received December 26, 2021; accepted April 15, 2022.

Article type: Peer-reviewed review article, open access (Dove Medical Press).

This patient-friendly article is based on peer-reviewed research. It summarizes findings from clinical trials and does not replace personalized medical advice from your oncology team. Treatment decisions should always be made in consultation with your healthcare providers.