Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities

Abstract

Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate that contains the irinotecan active metabolite, SN-38, linked to a humanized monoclonal antibody targeting trophoblast cell surface antigen 2, which is overexpressed in many solid tumors. In a basket design phase I/II study, sacituzumab govitecan demonstrated promising single-agent therapeutic activity in multiple cancer cohorts, leading to accelerated approval by the U.S. Food and Drug Administration of sacituzumab govitecan-hziy (TRODELVY) for the treatment of patients with metastatic triple-negative breast cancer who had received at least two prior therapies in the metastatic setting. Recently, results of the phase III trial, ASCENT, were confirmatory. There is limited available information on the adverse event management with sacituzumab govitecan needed to maximize the dose and duration of effective therapy while maintaining patient quality of life. This review summarizes the clinical development and the practical management of patients receiving sacituzumab govitecan. Sacituzumab govitecan has a well-defined and manageable toxicity profile, and rapid recognition and appropriate early and proactive management will allow clinicians to optimize sacituzumab govitecan treatment for patients.

Implications for Practice

Sacituzumab govitecan (TRODELVY) is a novel antibody-drug conjugate composed of the active metabolite of irinotecan (SN-38) conjugated to a monoclonal antibody targeting trophoblast cell surface antigen 2, an epithelial cell surface antigen overexpressed in many cancers. Because of the rapid approval of sacituzumab govitecan, there is limited available information on adverse event (AE) management with this agent. As such, this article reviews the clinical development of the drug, the AE profile, and provides recommendations regarding AE management to help optimize therapy with sacituzumab govitecan.

Breast cancer, Therapeutics, Antibody-drug conjugates, Toxicity

Background

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype defined by tumor cells that lack expression of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) [1–3]. TNBC accounts for approximately 15%–20% of diagnosed breast cancer cases and is associated with higher rates of visceral metastasis and cancer-related death [1, 4].

Current therapeutic options for metastatic TNBC (mTNBC) are limited, with sequential single-agent chemotherapy serving as the backbone of treatment [5–7]. These chemotherapy regimens, however, generally have low response rates, and early disease progression is common [1, 8]. Recent drug approvals for mTNBC include the PARP-inhibitors olaparib and talazoparib for patients with a germline BRCA mutation, as well as immunotherapy with a programmed cell death receptor ligand 1 (PD-L1) inhibitor, atezolizumab or pembrolizumab, in combination with chemotherapy, for patients whose tumors express PD-L1 [2, 3, 9, 10]. However, these therapies are restricted to certain populations [11]. Moreover, chemotherapy remains the mainstay after disease progression on these therapies. The median overall survival (OS) for mTNBC, which has not improved over the past 20 years, is 10–13 months and is significantly lower than the median OS for metastatic breast cancer overall (2.5–3 years) [12–15]. The combination of limited treatment options with aggressive tumor biology has made management of mTNBC particularly difficult, highlighting the need to identify novel systemic treatment options to improve outcomes for patients with mTNBC.

Antibody-drug conjugates (ADCs) are a relatively new class of biopharmaceutical drugs that consist of monoclonal antibodies chemically linked to highly potent cytotoxic drugs. Administered intravenously, ADCs function by first binding to a specific target protein on the tumor cell via its monoclonal antibody [16]. The cell then internalizes the ADC and the linker is cleaved, releasing the cytotoxic drug into the cell [16]. Unlike most standard chemotherapies, the ability to selectively target malignant cells has made ADCs a popular approach in cancer therapeutics in recent years [16]. To date, two anti-HER2 ADCs have been U.S. Food and Drug Administration (FDA) approved for the treatment of HER2-positive breast cancer, with several others in clinical trials. The first, trastuzumab emtansine, is approved for treatment of early and metastatic HER2-positive breast cancer [17, 18]. The second, trastuzumab deruxtecan, was recently approved for treatment of heavily pretreated HER2-positive metastatic breast cancer [19]. Although these ADCs have increased the availability of targeted therapies for patients with HER2+ breast cancer, the lack of standard molecular targets has limited the development of ADCs (and other targeted therapies) for TNBC.

Increased expression of trophoblast cell surface antigen 2 (Trop-2), a transmembrane calcium signal transducer, leads to tumor cell growth and has been identified in more than 85% of epithelial tumors, including TNBC [20, 21]. This discovery has led to the development and approval of sacituzumab govitecan, an ADC that targets Trop-2, for heavily pretreated mTNBC (Fig. 1). Sacituzumab govitecan uses a humanized anti–TROP-2 monoclonal antibody hRS7 IgG1κ to deliver SN-38, an active metabolite of irinotecan (topoisomerase I inhibitor), to malignant cells [22]. Unlike many other ADCs, sacituzumab govitecan uses a hydrolyzable CL2A linker such that SN-38 is delivered to both the targeted cell and its surrounding tumor microenvironment [23, 24]. This mechanism both minimizes off-target toxicity and creates a bystander effect that maximizes the drug's effect on complex tumors with cellular heterogeneity in Trop-2 expression [24].

Figure 1

Sacituzumab govitecan. Abbreviation: Trop-2, trophoblast cell surface antigen 2.

The accelerated approval of sacituzumab govitecan-hziy (TRODELVY) in April 2020 marked a breakthrough in breast cancer therapy as one of the few targeted therapy options currently available for TNBC. However, given its recent approval, there is limited experience using this drug in a clinical setting and, in particular, with managing adverse events. The aim of this review is to provide an overview of sacituzumab govitecan's development as well as to discuss its common toxicities and their clinical management.

Clinical Overview

IMMU-132-01 (NCT01631552) was a phase I/II, basket design, single-group, open-label, multicenter trial of sacituzumab govitecan in patients with previously treated advanced epithelial cancers [22]. After the phase I portion of the trial demonstrated manageable toxicities and promising efficacy in patients with mTNBC [22], the trial was expanded to include 69 patients with mTNBC, who were given sacituzumab govitecan intravenously at a dose of 10 mg/kg of body weight on days 1 and 8 of a 3-week treatment cycle [25]. Based on the positive results from these 69 patients, the FDA granted the drug “breakthrough therapy” status for treatment of patients with mTNBC who had received at least two prior therapies.

This trial was further expanded to a total of 108 patients with mTNBC receiving sacituzumab govitecan as a third-line or higher therapy [26]. The final objective response rate (ORR) was 33%, with 33 patients having partial response (PR) and 3 patients having complete response (CR). The median progression-free survival (PFS) was 5.5 (95% confidence interval [CI], 4.1–6.3) months, and the median OS was 13.0 (95% CI, 11.2–13.7) months. The median duration of treatment with sacituzumab govitecan was 5.1 months. This was approximately twice that of previous cancer treatments (2.5 months), highlighting the clinical activity of sacituzumab govitecan in patients with difficult-to-treat mTNBC [26]. Based on these positive results, in April 2020, the FDA granted accelerated approval to sacituzumab govitecan for treatment of patients with mTNBC who had received at least two prior therapies for metastatic disease. The recommended starting dose is 10 mg/kg administered intravenously once weekly on days 1 and 8 of continuous 21-day treatment cycles.

ASCENT was a phase III confirmatory, multicenter, randomized trial that compared sacituzumab govitecan with physician's choice of four single-agent chemotherapies (capecitabine, gemcitabine, vinorelbine, eribulin) in patients with mTNBC who have received at least two previous forms of chemotherapy. A total of 529 patients participated in the trial, with 267 patients receiving sacituzumab govitecan and 262 patients receiving treatment of physician's choice (TPC) [27]. The trial was halted early in March 2020 because of compelling evidence of efficacy. The ORR for the group treated with sacitzumab govitecan was 35% (4% CR, 31% PR), which was significantly higher than the ORR for the group treated with TPC (5%; 1% CR, 4% PR; p value < .0001) [27]. The median PFS for patients treated with sacituzumab govitecan and TPC was 5.6 (95% CI, 4.3–6.3) months and 1.7 (95% CI, 1.5–2.6) months, respectively, and the median OS was 12.1 (95% CI, 10.7–14.0) months and 6.7 (95% CI, 5.8–7.7) months, respectively [27].

There are several other ongoing clinical trials involving sacituzumab govitecan in the treatment of mTNBC as part of a combination therapy and in the neoadjuvant setting. Sacituzumab govitecan is also being studied in the treatment of ER-positive metastatic breast cancer. See Table 1 for a summary of ongoing trials.

Table 1

Ongoing Trials with Sacituzumab Govitecan

Trial	Phase	Study
NCT04230109 (NeoSTAR)	II	Response-guided Neoadjuvant Sacituzumab Govitecan (IMMU-132) in Patients With Localized TNBC
NCT04468061	II	Sacituzumab Govitecan With or Without Pembrolizumab in PD-L1-negative mTNBC
NCT04039230	I/II	Sacituzumab Govitecan in combination with Talazoparib for mTNBC
NCT03424005	Ib/II	Evaluating The Efficacy And Safety Of Multiple Immunotherapy-Based Treatment Combinations In Patients With Metastatic Triple-Negative Breast Cancer (Morpheus-TNBC)
NCT03901339 (TROPICS-02)	III	Sacituzumab Govitecan vs Physician's Choice in Subjects With HR+/HER2- MBC Who Have Failed at Least 2 Prior Chemotherapy Regimens
NCT04448886	II	Sacituzumab Govitecan With or Without Pembrolizumab in HR+ / HER2- MBC
NCT03992131	Ib/II	Open-label, Parallel Arm Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Oral Rucaparib in Combination With Other Anticancer Agents in Patients With a Solid Tumor

Pharmacology

As noted, sacituzumab govitecan is an ADC composed of a humanized RS7 antibody targeting Trop-2 linked with SN-38, a topoisomerase I inhibitor that is the active metabolite of irinotecan with 100–1000-fold increased potency compared with the parent drug [28, 29]. SN-38 interacts with topoisomerase I and prevents religation of topoisomerase I–induced single strand breaks, resulting in DNA damage that leads to apoptosis and cell death [30]. In addition to the direct cytotoxicity of SN-38, sacituzumab govitecan also results in antibody-dependent cellular cytotoxicity [31].

The pharmacokinetics of sacituzumab govitecan was explored in patients with various pretreated metastatic epithelial cancers in a phase I/II study [31]. Sacituzumab govitecan was administered at starting doses of either 8 mg/kg or 10 mg/kg intravenously on days 1 and 8 of 21-day cycles in the phase II component of the study, and it was observed that peak antibody concentrations typically increased proportionally with continued treatment in the 10 mg/kg group. Within 3 days of treatment, levels of SN-38 were largely cleared at a rate of ~50% per day [31]. No metabolism studies with sacituzumab govitecan have been conducted; however, SN-38 is metabolized via uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) [30]. Genetic variants of the UGT1A1 gene such as the UGT1A1*28 allele lead to reduced UGT1A1 enzyme activity [32]. Individuals who are homozygous for UGT1A1*28 allele are at increased risk for neutropenia from sacituzumab [30]. Approximately 20% of the Black or African American population, 10% of the White population, and 2% of the East Asian population may be affected [30]. Of the 84% of patients who received sacituzumab govitecan and had UGT1A1 genotype results, the incidence of grade 4 neutropenia was 26% in patients homozygous for the UGT1A1*28 allele, 13% in patients heterozygous for the UGT1A1*28 allele, and 11% in patients homozygous for the wild-type allele [30]. Routine UGT1A1 genotyping is not recommended prior to starting sacituzumab; however, patients who are known to have reduced UGT1A1 activity should be monitored closely for severe neutropenia [30]. The appropriate dose of patients who are UGT1A1*28 homozygous is currently not known and should be approached on an individual patient basis [30].

The half-life of sacituzumab govitecan was approximately 11–14 hours, whereas the half-life of the antibody was much longer, at approximately 103–114 hours [31]. Sacituzumab govitecan has a mean volume of distribution of 0.045 L/kg with a clearance rate of 0.002 L/kg per hour [30]. Renal elimination contributes minimally to the excretion of SN-38, and there are currently no data on the elimination of sacituzumab govitecan in patients with renal impairment (defined as creatinine clearance ≤30 mL/minute) [30]. Exposure of sacituzumab govitecan in patients with moderate or severe hepatic impairment is also unknown, but SN-38 exposure may be elevated in patients with decreased UGT1A1 activity [30]. Drug interactions studies were not conducted with sacituzumab govitecan; however, UGT1A1 inhibitors (such as glecaprevir and pibrentasvir) or inducers (such as rifampin and phenobarbital) are expected to increase or decrease SN-38 exposure, respectively, and the combination should be avoided [30].

Adverse Events Overview

The most common adverse events (AEs) in the 108 patients with mTNBC who received sacituzumab govitecan in the IMMU-132-01 trial were nausea (67%), diarrhea (62%), fatigue (55%), neutropenia (64%), and anemia (50%) [26]. The most common grade 3 or higher AEs were neutropenia, anemia, and decreased white-cell count. Serious AEs (which include AEs that are life-threatening, require intervention to prevent permanent damage, require hospitalization, or result in death), which occurred in 35 patients (32%), included febrile neutropenia (7%), vomiting (6%), nausea (4%), diarrhea (3%), and dyspnea (3%). No patients experienced severe drug-related neuropathy or cardiac adverse events during treatment. The mean number of cycles administered was 9.6 (18.7 doses). Forty-eight out of the 108 patients (44%) temporarily halted treatment because of AEs, most commonly neutropenia, and 3 patients (2.8%) were required to discontinue treatment. There were four deaths during treatment [26].

In the ASCENT phase III trial, the median number of treatments for patients receiving sacituzumab govitecan was 7, and the median treatment duration was 4.4 months [27]. The most common AEs associated with sacituzumab govitecan, summarized in Figure 2, were neutropenia (63%), diarrhea (59%), nausea (57%), alopecia (46%), fatigue (45%), and anemia (34%). There were no severe cardiovascular toxicity and no treatment-related deaths with sacituzumab govitecan. The discontinuation rate caused by AEs associated with sacituzumab govitecan was 4.7%, whereas the discontinuation rate associated with TPC was 5.4% [27].

Figure 2

Adverse events observed in the randomized phase III clinical trial (ASCENT) [27]. Grading based on National Cancer Institute Common Terminology Criteria for Adverse Events. Abbreviations: SG, sacituzumab govitecan; TPC, treatment of physician's choice.

Importantly, efficacy outcomes for patients with dose reduction or interruption in the sacituzumab govitecan arm of ASCENT were similar to those for the overall population [33]. Patients who had dose reductions with SG had median PFS of 8.3 months (95% CI, 5.4–10.3 months), which was similar to the overall study (median PFS, 5.6 months; 95% CI, 4.3–6.3 months). Similarly, although dose reductions were more frequent in patients 65 and older, there was no considerable impact on efficacy outcomes were observed [34]. Patients aged ≥65 years who received SG had a significant survival and clinical benefit versus TPC with median PFS, 7.1 versus 2.4 months, comparable in the overall study population [34]. In patients aged ≥65 years, key grade ≥ 3 treatment-related AEs (SG vs. TPC) were neutropenia (45% vs 40%), anemia (14% vs. 6%), leukopenia (10% vs. 4%), diarrhea (10% vs. 0%), and febrile neutropenia (8% vs. 0%), comparable with the safety profile in the overall study population [34].

Preventing and Managing Adverse Events

Nausea/Vomiting

Sacituzumab govitecan is moderately emetogenic (>30% to 90% risk of emesis) [30, 35]. As per FDA label and National Comprehensive Cancer Network guidelines for moderately emetogenic regimen, patients should be premedicated prior to each infusion starting with a standard two-drug regimen consisting of a 5-HT3 antagonist and dexamethasone on day 1 [35]. NK-1 antagonists may also be considered as part of a three-drug regimen in patients at higher risk of chemotherapy-induced nausea and vomiting (CINV) or for those who have refractory CINV [35]. Additional as-needed take-home medications (such as ondansetron or prochlorperazine) for CINV prevention and treatment should also be offered to patients [35]. Olanzapine can also be considered for persistent or anticipatory nausea [35].

Hypersensitivity Reactions

Serious and life-threatening hypersensitivity reactions (HSRs) have been reported with sacituzumab govitecan. Per the manufacturer, HSRs within 24 hours occurred in 37% (151/408) of patients, with 1% occurring as grade 3–4 [30]. Given that more than one-third of patients experienced HSRs, it is advised to also premedicate with an antipyretic and H1 and H2 blockers prior to each infusion [30]. Additional corticosteroids may be considered for patients who have had prior infusion reactions [30]. Patients should be observed for infusion-related complications during each infusion and for at least 30 minutes following the end of infusion. Emergency equipment and medications to manage reactions should be available for immediate use. It is important to counsel patients to call if they experience facial, lip, tongue, or throat swelling, urticaria, difficulty breathing, lightheadedness, dizziness, chills, rigors, wheezing, pruritus, flushing, rash, hypotension, or fever that occurs during or within 24 hours of the infusion [30].

Diarrhea and Cholinergic Syndrome

Sacituzumab govitecan can cause severe diarrhea, which could be due to either early cholinergic syndrome or delayed diarrhea due to SN-38. As per FDA label, if a patient develops signs of acute diarrhea or early cholinergic syndrome (abdominal cramping, diarrhea, sweating, or excessive salivation) during or shortly after infusion, they should be treated with atropine 0.4 mg intravenous (IV) every 15 minutes for two doses if required [30]. Subsequent doses of atropine 0.2 mg IV may also be administered, for a total of 1 mg. Additional prophylaxis with atropine should be used for future infusions.

Routine prophylaxis is not routinely used nor recommended in patients who have not previously experienced diarrhea. At the onset of delayed diarrhea, patients should be evaluated for infectious causes. If ruled negative, promptly initiate one dose of loperamide 4 mg p.o. The labeling for sacituzumab govitecan recommends following the initial dose of loperamide with 2 mg p.o. after every additional episode of diarrhea for a maximum of 16 mg/day and discontinue after 12 hours have elapsed from last episode of diarrhea [30] Alternative high-dose loperamide recommendations (2 mg every 2 hours or 4 mg every 4 hours at night) have been used successfully for irinotecan-related diarrhea in patients with colorectal cancer and may be considered in cases of severe diarrhea. Loperamide has minimal systemic absorption and is excreted in stool, so the risk of overdose is unlikely [30, 36, 37]. Patients should also be advised to call immediately if black or bloody stools, symptoms of dehydration, inability to take fluids by mouth because of nausea, or vomiting or diarrhea within 24 hours of initiating supportive measures. See Figure 3 for a summary of diarrhea management.

Figure 3

Management of sacituzumab govitecan–induced diarrhea [27,30]. *Always consider infectious causes of diarrhea. IV, intravenous; SC, subcutaneously; TID, three times daily.

Neutropenia

Sacituzumab govitecan can also cause severe or life-threatening neutropenia. Febrile neutropenia occurred in 6% patients treated with sacituzumab, including 8% patients with mTNBC after at least two prior therapies [30]. Less than 1% of patients had febrile neutropenia leading to permanent discontinuation in initial studies [30]. Anemia and thrombocytopenia have also occurred.

Consistent with the guidelines in the clinical trials, including ASCENT [27], routine primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) support is not recommended, but secondary prophylaxis could be considered at the first occurrence of grade 4 neutropenia lasting 7 or more days, grade 3 febrile neutropenia, or grade 3–4 neutropenia that has delayed dosing by 2 or 3 weeks for recovery to grade ≤ 1. If the neutropenia presents on day 1, consider use of a daily G-CSF (filgrastim or biosimilar) on days 4 and 5 or days 4 through 6, avoiding use 24 hours before or after sacituzumab govitecan infusion. If the neutropenia presents on day 8, pegylated G-CSF (pegfilgrastim or biosimilar) may be considered 24–48 hours postinfusion. See Table 2 and Figure 4 for a summary of sacituzumab govitecan dose reduction recommendations in the setting of neutropenia [30].

Table 2

Recommended dose modification schedule for sacituzumab govitecan

Event (NCI CTCAE grading)	Occurrence	Recommended dose reduction or action
Severe neutropeniaa
Grade 4 neutropenia (ANC <500/mm3) ≥7 days; or grade 3 febrile neutropenia (ANC <1000/mm3 and fever ≥38.5°C); or at time of scheduled treatment; grade 3–4 neutropenia which delays dosing by 2 or 3 wk for recovery to grade ≤ 1	First	25% dose reduction (to 7.5 mg/m2) and administer G-CSF
	Second	Reduce dose to 5 mg/m2 (50% reduction)
	Third	Discontinue treatment
At time of scheduled treatment, grade ≥ 3 neutropenia which delays dosing beyond 3 wk for recovery to grade ≤ 1	First	Discontinue treatment
Severe nonneutropenic toxicity
Grade 4 nonhematologic toxicity of any duration; or any grade 3–4 nausea, vomiting, or diarrhea due to treatment that is not controlled with antiemetics and antidiarrheal agents; or other grade 3–4 nonhematologic toxicity persisting >48 hr despite optimal medical management; or at time of scheduled treatment, grade 3–4 nonneutropenic hematologic or nonhematologic toxicity, which delays dose by 2 or 3 wk for recovery to grade ≤ 1	First	Reduce dose to 7.5 mg/m2 (25% reduction)
	Second	Reduce dose to 5 mg/m2 (50% reduction)
	Third	Discontinue treatment
In the event of grade 3–4 nonneutropenic hematologic or nonhematologic toxicity, which does not recover to grade ≤ 1 within 3 wk	First	Discontinue treatment

From ref. [27, 30].

^aWithhold sacituzumab govitecan for absolute neutrophil count (ANC) <1500/mm on day 1 of any cycle, if ANC <1000/mm³ on day 8 of any cycle, or for neutropenic fever. Do not reescalate the sacituzumab govitecan dose after a dose reduction for toxicity has been made.

Abbreviations: ANC, absolute neutrophil count; G-CSF, granulocyte colony-stimulating factor; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events.

Figure 4

Management of sacituzumab govitecan-induced neutropenia. [27,30]. Abbreviations: ANC, absolute neutrophil count; G-CSF, granulocyte colony-stimulating factor; SG, sacituzumab govitecan.

Rash

Rash can present as maculopapular, erythematous, generalized, acneiform, irritative or exfoliative in nature, and pruritic [30]. Use of topical corticosteroid application and oral antihistamines are the preferred management strategies. Dermatology referral can also be considered.

Alopecia

Alopecia has been reported in patients who received sacituzumab govitecan, possibly because of SN-38 backbone [27]. Patients should be informed of this adverse effect and be provided a prescription for a wig if interested. The impact of scalp-cooling devices has not been thoroughly studied, and further research is needed to evaluate the efficacy of different scalp-cooling devices to prevent and/or reduce sacituzumab govitecan-induced alopecia.

Other Toxicities

Additional dose reductions for severe nonneutropenic toxicity are also recommended (see Table 2) [30]. For the first grade 4 nonhematologic toxicity of any duration, any grade 3 or 4 nausea, vomiting, or diarrhea that is not controlled with antiemetics or antidiarrheal agents; any grade 3 or 4 nonhematologic toxicity lasting longer than 48 hours despite optimal management; or any grade 3–4 nonhematologic toxicity that delays dosing by 2–3 weeks for recovery to grade ≤ 1, sacituzumab govitecan should be dose reduced by 25%. Second episodes should be dose reduced by 50%. For third occurrences or any grade 3–4 nonneutropenic hematologic or nonhematologic toxicity that does not recover to grade ≤ 1 within 3 weeks, sacituzumab should be permanently discontinued.

Conclusion

Sacituzumab govitecan is an effective and generally well-tolerated agent that represents a promising novel therapy for patients with mTNBC. The most common adverse effects observed in patients with mTNBC treated with sacituzumab govitecan parallel those of chemotherapy and can be manageable with early, proactive intervention. The proper monitoring and early management of adverse effects associated with sacituzumab govitecan will allow patients to stay on their treatment schedule, not only to maintain adequate levels of an effective drug in the body but also to preserve overall patient quality of life. Ongoing trials are exploring sacituzumab govitecan in other disease settings, including early breast cancer.

For Further Reading: Shen Zhao, Ding Ma, Yi Xiao et al. Molecular Subtyping of Triple-Negative Breast Cancers by Immunohistochemistry: Molecular Basis and Clinical Relevance. The Oncologist 2020;25:e1481–e1491.

Implications for Practice: An immunohistochemistry (IHC)-based classification approach was developed for triple-negative breast cancer (TNBC), which exhibited substantial agreement with the mRNA expression-based classification. This IHC-based classification (a) allows for subgrouping of TNBC patients in large clinical trials and evaluating the efficacy of targeted therapies within certain subtypes, (b) will contribute to the practical application of subtype-specific treatment for patients with TNBC, and (c) can provide additional information beyond traditional prognostic factors in relapse prediction.

Acknowledgments

Dr. Spring is supported by National Cancer Institute grant K12CA087723, Terri Brodeur Breast Cancer Foundation grant, Breast Cancer Alliance grant, and a Massachusetts General Hospital ESCCO Breast Cancer Research Fund grant.

Author Contributions

Conception/design: Laura M. Spring, Beverly Moy, Aditya Bardia

Data analysis and interpretation: Laura M. Spring, Erika Nakajima, Jennifer Hutchinson, Elene Viscosi, Gayle Blouin, Colin Weekes, Hope Rugo, Beverly Moy, Aditya Bardia

Manuscript writing: Laura M. Spring, Erika Nakajima, Jennifer Hutchinson, Elene Viscosi, Gayle Blouin, Colin Weekes, Hope Rugo, Beverly Moy, Aditya Bardia

Final approval of manuscript: Laura M. Spring, Erika Nakajima, Jennifer Hutchinson, Elene Viscosi, Gayle Blouin, Colin Weekes, Hope Rugo, Beverly Moy, Aditya Bardia

Disclosures

Laura M. Spring: Novartis, Puma, Lumicell, Avrobio (C/A), Tesaro, Merck (RF), Tesaro, Merck (Other–Travel support); Hope Rugo: Immunomedics, Odonate, Roche, Sermonix, Risa I, Eli Lilly & Co, Novartis, Boehringer Ingelheim, Pfizer, Daiichi, Macrogenics, Astra Zeneca, Seattle Genetics (RF), Samsung, Puma (C/A); Aditya Bardia: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Taiho, Sanofi, Diiachi Pharma/Astra Zeneca, Puma, Biothernostics Inc., Phillips, Eli Lilly & Co, Foundation Medicine (C/A), Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, Diiachi Pharma/Astra Zeneca (RF–Institution). The other authors indicated no financial relationships.

(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/inventor/patent holder; (SAB) Scientific advisory board

Author notes

Contributed equally.

Disclosures of potential conflicts of interest may be found at the end of this article.

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