Advances in the field of breast cancer continue to posit questions that require further evaluation, according to Jamie Carroll, APRN, CNP, MSN.

Specifically, the the RIGHT Choice (NCT03839823) study as well as the CARRIERS study, both of which were presented at the 2022 San Antonio Breast Cancer Symposium have generated discourse regarding the use of the findings.

For instance, although the RIGHT Choice study demonstrated an improvement in progression-free survival (PFS) for pre/perimenopausal patients with aggressive hormone receptor–positive and HER2-negative advanced breast cancer receiving ribociclib (Kisqali) and endocrine therapy (ET) compared with a chemotherapy combination, both arms achieved similar overall response rates (ORR).

“[The] investigator’s choice chemotherapy options are interesting because they’re not typical chemotherapy combinations that we use especially in first line metastatic breast cancer,” Carroll, a nurse practitioner at Mayo Clinic in Rochester Minnesota, said in an interview with 

 “There are things that you can pull from this study, but I don’t think that it’s going to be practice changing.”

In the RIGHT Choice study, median PFS was 24 months for the ribociclib and endocrine therapy arm (n = 112) compared with 12.3 months in the combination chemotherapy arm (n = 110; HR, 0.54). Median time to treatment failure was 18.6 months vs 8.5 months, respectively (HR, 0.45). Treatment related serious adverse events were lower in the ribociclib and endocrine therapy group with 1.8% of patients experiencing a serious event of all grades compared with 8.0% of the combination chemotherapy group; discontinuation rates were 7.1% and 23.0%, respectively.

The CARRIERS study sought to determine the risk of developing contralateral breast cancer for patients with the germline pathogenic variants 

. Findings showed that patients with ER-negative disease with 

 mutations had a higher risk level for developing contralateral breast cancer, and patients with 

 mutations overall and those with ER-positive disease did not.

Sequencing to identify germline pathogenic variants from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium examined variants in 32,247 patients with breast cancer and 32,544 women who were unaffected.

After a median follow-up of 11 years, patients in the CARRIER study experienced 10-year cumulative incidence of contralateral breast cancer at rates vs noncarriers of 

 ER-negative (5.4% vs 19.7%). The CARRIERS study demonstrated that patients with 

mutations are at an increased risk for contralateral breast cancer similar to patients with 

Carroll discussed the 2 trials that were presented at SABCS and how their efficacy data may or may not effect practice.

®:Please discuss the RIGHT Choice trial.

:This was a phase 2 study that came out of Taiwan looking at patients with aggressive hormone receptor–positive, HER2-negative advanced breast cancer treated with ribociclib and endocrine therapy vs physicians’ choice combination chemotherapy. These were patients [with] either relapsed breast cancer or de novo stage 4 breast cancer and so [investigators] were looking at patients that had symptomatic visceral metastasis, rapid disease progression or impending visceral compromise, or marked symptomatic nonvisceral disease.

It was looking at: what’s the right choice? For patients who have visceral crisis, do we give them physician’s choice chemotherapy vs ribociclib plus aromatase inhibitor [AI] and then goserelin if they’re premenopausal? Do you need a response quickly or is endocrine therapy our mainstay of treatment regardless of visceral crisis or symptomatic assessment of the patient?

With the RIGHT Choice study design, patients could be either pre or perimenopausal. [Patients had] hormone receptor–positive, HER2-negative measurable disease by RECIST [1.1 criteria], an ECOG performance status of 2 or less, and total bilirubin less than or equal to 1.5—the upper limits of normal. IT was a 1:1 randomization with the CDK4/6 plus AI and investigator’s choice of chemotherapy. [Chemotherapy] combinations [included] docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine.

What was notable about the RIGHT Choice trial?

Right away the study design is interesting to me because it’s subjective information and not necessarily objective when you're looking at patients calling it ‘aggressive disease.’ If they’re symptomatic visceral metastasis, that makes sense—they have symptoms, but is the symptom related to burden of disease in their liver? Or are they feeling that capsular push and pressure on their liver, and calling it visceral crisis? If total bilirubin is less than 1.5—the upper limits of normal—is that a visceral crisis?To me, it’s very subjective with the inclusion criteria.

[The] primary end point [investigators] looked at was PFS. Off the bat, we already know that CDK4/6 [inhibitor] ribociclib plus AI has a [median] PFS of 24 months and chemotherapy tends to be less than that.

The question still remains: did patients have a reduction of their disease quicker with chemotherapy vs CDK4/6 and AI? The ORRs were pretty similar, 65% with the ET arm and 60% with the chemotherapy arm; the study wasn’t powered for overall response.

Siddhartha Yadav, MD, who is a Mayo Clinic oncologist, presented on the CARRIERS study—where [investigators] are looking at contralateral breast cancer risk among carriers of germline pathogenic variants in 

have elevated risk and so supplemental breast imaging is recommended if they do not have bilateral mastectomy, but contralateral breast cancer after a primary breast cancer [is not well-defined], and in the past [has primarily been] looked for in women with 

The CARRIERS study was looking at 32,000 women with a breast cancer diagnosis and then 32,000 matched women that are unaffected as controls. There were 15,000 women with unilateral invasive breast cancer looking at 10 prospective studies in the United States. The inclusion criteria was a preserved contralateral breast and at least 1 year of follow-up. Exclusion was patients who had ductal carcinoma in situ at initial diagnosis. Seventy-three percent [of patients] were postmenopausal at diagnosis which goes along with the median age at 62 years, and 75% of those patients had ER-positive breast cancer and 46% adjuvant endocrine therapy use.

What were the main findings from the CARRIERS study?

Median follow-up was 11 years and Yadav broke down the events by gene. The noncarriers genes events number was 711 out of the 14,444 patients and each one of the genes he broke down on contralateral breast cancer events [was as follows]: 

0.6 events, so less than the noncarriers.

[Yadav] looked at overall and ER status of a first breast cancer and the incidence of breast cancer from the first breast cancer diagnosis. The overall 

carrier has a 3% risk of a contralateral breast cancer; 

 was 23% over those 10 years of a contralateral breast cancer and 

[-mutant disease]had 2 times the risk of a subsequent breast cancer­—with their second breast cancer being ER-negative, regardless of what the first breast cancer was. That was interesting because if somebody has an ER-positive breast cancer and a 

mutation they’re going to be on endocrine therapy, but they still have 2 times the risk of developing a contralateral breast cancer.

It was interesting when they talked about the contralateral breast cancer risk in women over the age of 65 years at first breast cancer diagnosis. The number of contralateral breast cancers in those pathogenic variant carriers was 3 with 6010 women. If you have an 80-year-old whose first breast cancer was diagnosed and she’s got contralateral tissue, then maybe [supplemental breast imaging] does not do her benefit because 3 out of 6000 women is not a very high number.

Can you discuss how this might translate into practice and conversations with patients about breast imaging and what this could mean?



For patients that choose wide local excision or breast conserving therapy and not a contralateral mastectomy, it’s helpful to tell them what their risk of a secondary breast malignancy is in their pathogenic variant subtype because in the past we’ve always said,“Yes, you need a contralateral mastectomy.”

It’s helpful to understand that if they have a 

mutation they're at 2 times the increased risk of an ER-negative breast cancer, but not necessarily an ER-positive breast cancer. 

 mutations do not increase the risk of a contralateral breast cancer, so for those patients, you may not necessarily need a contralateral mastectomy if you’re not at increased risk of a contralateral breast cancer.

Yadav S, Boddicker NJ, Na J, et al. Population-based estimates of contralateral breast cancer risk among carriers of germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract GS4-04.

Hu C, Hart SN, Gnanaolivu R, et al. A population-based study of genes previously implicated in breast cancer. 

. 2021;384(5):440-451. doi:10.1056/NEJMoa2005936

Articles

Jamie Carroll, APRN, CNP, MSN, offers her perspective on emerging data from the 2022 San Antonio Breast Cancer Symposium. 

Carroll Highlights Data Presented at SABCS from the CARRIERS and RIGHT Choice Studies

, we interview 2 nurse practitioners about their key takeaways from the 2022 San Antonio Breast Cancer Symposium (SABCS).

“As time goes [on], we learn more,” says Loyda Braithwaite, MSN, RN, AGPCNP-BC, AOCN. Specifically, as more safety data with 

 (Enerhtu) comes to light, providers are getting a better idea of how to anticipate and handle potentially serious adverse events such as interstitial lung disease and left ventricular dysfunction

Braithwaite, who is an oncology nurse practitioner at the University of Wisconsin Carbone Cancer Center in Madison, highlights exciting developments in HER2-positive breast cancer and for patients with metastatic disease, as well as the potential benefit of oral selective estrogen receptors degraders, throughout the discussion.

Moreover, according to Jamie Carroll, APRN, CNP, MSN, a nurse practitioner at Mayo Clinic in Rochester, Minnesota, data presented at the meeting may change patient conversations in the adjuvant setting. Findings from the POSITIVE (NCT02308085) trial suggest that pausing adjuvant endocrine therapy may be safe for women with hormone receptor–positive breast cancer who wish to pursue pregnancy.

“It's a common discussion that we have and it’s helpful to know that the POSITIVE trial did not see that disrupting endocrine therapy impacted disease outcomes,” Carroll says. “That’s helpful for patients and providers to know that they’re not seeing an increase in recurrence when endocrine therapy is paused to achieve pregnancy.”

Interested in learning more from SABCS? Check out our coverage of the conference 

We want to hear from you! Which data from SABCS do you think will be practice changing? Email 

Sarah Donahue Highlights Destiny-Breast04 Trial Takeaways for Patients With HR+, HER2-Low Metastatic Breast Cancer

Sri Kota Weighs in On the Evolving Breast Cancer Paradigm

Emerging Data Showcases Promising Advancements for Patients With HER2-Low Breast Cancer

POSITIVE Study Findings Shift Conversations on Pregnancy in ER+ Breast Cancer

CBD Oil Shows Modest Improvements in Tamoxifen-Related Adverse Effects

Antidiarrheal Prophylaxis Remains a Key Focus in TKI Treatment for Patients with HER2+ Breast Cancer

Real-World Data Show Neoadjuvant Pertuzumab/Trastuzumab Increases pCR Rates in HER2+ Breast Cancer

Grace Choong and Matthew Goetz On the Impact of Adjuvant Endocrine Therapy Omission in ER+ Positive Breast Cancer

Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated survival results of the randomized, phase 3 study DESTINY-Breast03. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX.

Krop, Ian et al T-DXd yields superior outcomes over chemotherapy-based regimens in patients previously treated with T-DM1 participating in the phase III DESTINY-Breast02 trial. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX.

Rugo HS, Bardia A, Marmé F, et al. Sacituzumab govitecan vs treatment of physician’s choice: efficacy by Trop-2 expression in the TROPiCS-02 study of patients with HR+/HER2– metastatic breast cancer. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX.

Hurvitz S, Wang LS, McAndrew NP, et al. TRIO-US B-12 TALENT: neoadjuvant trastuzumab deruxtecan (T-DXd) with or without anastrozole for HER2-low, HR+ early-stage breast cancer. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX.

Bardia A, Bidard FC, Neven P, et al. EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+/HER2- metastatic breast cancer: updated results by duration of prior CDK4/6i in metastatic setting. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX.

Partridge A, Niman SM, Ruggeri M, et al. Pregnancy outcome and safety of interrupting therapy for women with endocrine responsIVE breast cancer: primary results from the POSITIVE trial (IBCSG 48-14 / BIG 8-13). Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX.

Podcasts

Loyda Braithwaite, MSN, RN, AGPCNP-BC, AOCNP; and Jamie Carroll, APRN, CNP, MSN, highlight presentations from the 2022 San Antonio Breast Cancer Symposium that will influence oncology nursing practice. 

Nurse Practitioners Weigh in on Data From the San Antonio Breast Cancer Symposium

The 2022 San Antonio Breast Cancer Symposium highlighted promising advances in breast cancer treatments across multiple settings and disease types, including for patients with HER2-low and hormone receptor–negative disease.

Moreover, according to Loyda Braithwaite, MSN, RN, AGPCNP-BC, AOCNP, some data that were presented may hold the potential to open doors for patients with hard-to-treat diseases.

Braithwaite, who is an Oncology Nurse Practitioner at the University of Wisconsin Carbone Cancer Center, recently sat down with 

 to offer her perspective on key trials that were presented at this year’s symposium.

 What stood out to you about this year’s symposium?

 What I found very interesting is how much we are discovering within the HER2-positive population. This is [a space] that has been kind of stagnant for a few years, but now more data from the 

 [NCT03529110] [trials, are] confirming what we previously knew with TDX-d [fam-trastuzumab deruxtecan-nxki (Enhertu)]. I think this is very informative. Data are maturing more, and we’re seeing the advantages in progression-free survival [PFS] for our patients with HER2-positive metastatic breast cancer. When it comes to the metastatic setting, sometimes, we are left with [few] options, but I think [the data from these trials] are good and interesting.

As time goes, we learn more. As we treat more patients with TDX-d, [we are] more aware of some of the adverse effects, particularly with pulmonary involvement, or [interstitial lung disease] ILD. When CDK4/6 inhibitors came, we knew that there was the risk of ILD and pulmonary compromise, but now with more patients being treated with TDX-d, I think those rates have a risk of increasing or being more common, so we have to be on top of that early on.

On top of the ILD, [another] severity was the left ventricular dysfunction [LVEF] for patients. As clinicians, we have to be on the lookout for potentially life threatening or pretty severe [adverse effects, such as] ILD and LVEF dysfunction.

Were there any other trials that are promising to open doors for hard-to-treat populations?

I found sacituzumab govitecan-hziy [Trodelvy], in TROPiCS-02 [NCT03901339] for patients with hormone receptor–positive disease [to be interesting]. We’ve known about [this drug’s efficacy] for triple negative disease in the metastatic setting, but now we’re seeing it for patients with hormone receptor–positive [disease] too. We saw some data that, regardless of TROP-2 expression, there may be some benefit for these patients as well, in terms of PFS. This is just shining light on potentially more treatments for patients with hormone receptor–positive breast cancer and which we didn’t have in the past. 

Another trial that I think was very fascinating was the 

 [NCT04553770]. That was looking at whole new world of HER2-low. To me, this is magnificent because it’s opening this door. [We] have all these patients [whose HER2-low disease] we can [now] target.

This particular trial was looking into TDX-d alone and TDX-d with endocrine therapy for patients with HER2-low and hormone receptor–positive [disease] in the neoadjuvant setting. Before, we had options with neoadjuvant therapy and endocrine therapy alone, and [we’d] see how it responds, but sometimes we were missing those people that may have been high risk. [Although] the data is still not fully mature, it seems promising that we may be able to, in the future, use TDX-d in the neoadjuvant setting—potentially as a single therapy, or in a combination with [another] therapy. I really liked that.

How do you interpret the data surrounding oral SERDS? Do they hold potential to change practice?

Oral [selective estrogen receptor degraders] SERDs were a big thing in San Antonio this year. [Although] the AMEERA-3 [NCT04059484] didn’t meet its primary end point, the EMERALD trial [NCT03778931] with elacestrant did have some positive data that may be promising. In combination with a CDK4/6 inhibitor it looks promising, as well.

For decades, we have had fulvestrant but administration [was difficult, so I believe] SERDs could be practice changing. If we had oral SERDs approved—when it comes to having an extra line of endocrine therapy for patients or an option that does not require traveling for patients—access would be better. [Right now,] patients commute every month to get a health care professional to administer an injection.

As the data matures, I can only imagine other trials will come down the pipe[line]. So, to me, this is very exciting from the clinician perspective, but also from the patient perspective, to think about the accessibility [options] that we’re going to have to treat them.

Loyda Braithwaite, MSN, RN, AGPCNP-BC, AOCNP, reflects on data presented at the San Antonio Breast Cancer Symposium.

Regardless of Trop-2 expression, patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer achieved better survival outcomes with sacituzumab govitecan-hziy (Trodelvy) compared with treatment of physician’s choice (TPC), according to updated findings from the phase 3 TROPiCS-02 trial (NCT03901339).

“We found that there was an improvement in progression-free and overall survival regardless of whether you fell into the lower Trop-2 expression or higher Trop-2 expression [group],” Hope S. Rugo, MD, professor of medicine and director of breast oncology and clinical trials education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, said during a presentation of the findings at the 2022 San Antonio Breast Cancer Symposium.

Sacituzumab govitecan is a first-in-class Trop-2–directed antibody-drug conjugate (ADC), which has already been approved for use in patients with locally advanced or metastatic triple-negative breast cancer who have received at least 2 prior systemic therapies.

High expression of Trop-2, an epithelial antigen, is reported in about 85% to 90% of all subtypes of breast cancer.

Sacituzumab govitecan has already demonstrated efficacy in patients with hormone receptor–positive, HER2-negative metastatic breast cancer in earlier results from the TROPiCS-02 trial. Results from the first interim analysis presented at the 2022 American Society for Clinical Oncology Annual Meeting showed that the median PFS was 5.5 months with sacituzumab govitecan (n = 272) vs 4.0 months with TPC (n = 271; HR, 0.66; 95% CI, 0.53-0.83; 

At the European Society for Medical Oncology Congress 2022, findings from the second interim analysis demonstrated that the median OS was 14.4 months with sacituzumab govitecan compared with 11.2 months with TPC (HR, 0.79; 95% CI, 0.65-0.96; 

 The objective response rate (ORR) was 21% with the ADC compared with 14% with TPC (odds ratio, 1.63; 95% CI, 1.03-2.56; 

 expression was determined on primary or metastatic archival tumor tissue samples using a validated immunohistochemistry assay. Patients were given an H-score to represent the total percent staining weighted by the intensity of the staining (range, 0-300).

Eighty-eight percent of the investigational arm and 83% of the control arm had evaluable samples for Trop-2 level testing. Overall, 5% of patients had an H-score of 0, 12% had a score between 0 and 10, 24% had a score between 10 and 100, and 58% had a score of at least 100.

Among patients with Trop-2 expression of 100 or more, the median PFS was 6.4 months (95% CI, 4.0-8.3) with sacituzumab govitecan and 4.1 months (95% CI, 2.1-4.5) with TPC (HR, 0.60; 95% CI, 0.44-0.81). In those with an H-score below 100, the median PFS was 5.3 months (95% CI, 4.1-6.0) in the sacituzumab govitecan arm and 4.0 months (95% CI, 2.8-5.6) in the TPC arm (HR, 0.77; 95% CI, 0.54-1.09). More specifically, the median PFS in patients with a score of 10 or below was 5.5 months (95% CI, 2.8-9.5) with the ADC and 4.3 months (95% CI, 1.7-6.4) with standard therapy (HR, 0.89; 95% CI, 0.51-1.57), and for those with a score between 10 and 100, the median PFS was 5.0 months (95% CI, 4.1-7.1) and 3.5 months (95% CI, 1.6-5.6), respectively (HR, 0.67; 95% CI, 0.42-1.07).

Median OS in patients with a Trop-2 expression of 100 or more was 14.4 months (95% CI, 12.7-16.4) with sacituzumab govitecan and 11.2 months (95% CI, 9.9-12.9) with TPC (HR, 0.83; 95% CI, 0.62-1.11). Patients with a score below 100 had a median OS of 14.6 months (95% CI, 12.7-18.1) with the ADC and 11.3 months (95% CI, 10.0-13.3) with standard therapy (HR, 0.75; 95% CI, 0.54-1.04). More specifically, among patients with a score of 10 or below, the median OS was 17.6 months (95% CI, 11.5-not evaluable) with sacituzumab govitecan compared with 12.3 months (95% CI, 8.0-15.3) with TPC (HR, 0.61; 95% CI, 0.34-1.08), and for those with a score between 10 and 100, the median OS was 13.7 months (95% CI, 10.9-16.3) and 11.0 months (95% CI, 9.0-13.5), respectively (HR, 0.81; 95% CI, 0.54-1.23).

“It appeared there was a PFS and OS benefit in these very low scores, with a H-score up to 10—Trop-2 expression didn’t impact response or safety as well. [I believe] that confirms the fact that sacituzumab is effective regardless of Trop-2 expression, and that you don’t need to test for Trop-2 to determine which patients are eligible for benefit from sacituzumab,” Rugo said, though she noted in her presentation that the sample size was small and so caution should be given to interpreting these data.

In patients with a score of up to 10, the ORR was 24% and the clinical benefit rate (CBR) was 32%. The median duration of response (DOR) in this subgroup was 7.5 months (95% CI, 2.5-not reached [NR]). In the 10 to 100 Trop-2 expression level group, the ORR was 18%, the CBR was 27%, and the median DOR was 7.4 months (95% CI, 4.1-NR). In the 100 or more expression level group, the ORR was 23%, the CBR was 39%, and the median DOR was 8.5 months (95% CI, 5.9-16.9).

The safety profile by treatment was not impacted by Trop-2 expression levels. With sacituzumab govitecan specifically, the rate of grade 3 or higher treatment-emergent adverse events (TEAEs) was 79% in patients with an H-score below 100 and 74% in those with a score of 100 or higher. TEAEs led to treatment discontinuation in 2% of patients with a score below 100 and 8% with a score of at least 100. Serious TEAEs were reported in 26% of patients with a score below 100 and in 30% with a score of at least 100; TEAEs led to death in 1% and 3% of patients, respectively.

Neutropenia of grade 3 or higher was reported in 58% and 54% of patients in the sacituzumab govitecan arm who had H-scores below and above 100, respectively, and in 46% and 35% of patients in the TPC arm. Grade 3 or higher febrile neutropenia was observed in 7% and 6% of patients in the sacituzumab govitecan arm who had H-scores below and above 100, respectively, and in 4% and 5% of patients in the TPC arm. Diarrhea of grade 3 or higher was reported in 10% and 9% of patients in the sacituzumab govitecan arm who had H-scores below and above 100, respectively, and in 1% of patients in each group in the TPC arm.

TROPiCS-02 is a randomized, open-label phase 3 study that enrolled 543 patients with locally recurrent or metastatic, inoperable hormone receptor–positive, HER2-negative breast cancer that has progressed after at least 1 prior endocrine therapy, a taxane, and a CDK4/6 inhibitor in any setting. Patients had received between 2 and 4 prior lines of chemotherapy for metastatic disease.

Enrolled patients were randomly assigned 1:1 to intravenous sacituzumab govitecan at 10 mg/kg administered on days 1 and 8 of every 3-week cycle or TPC, which consisted of capecitabine, vinorelbine, gemcitabine, or eribulin. Patients were stratified by the presence of visceral metastases, endocrine therapy use in the metastatic setting at 6 months or more, and the number of prior lines of chemotherapy.

The primary end point was PFS by blinded independent central review. Secondary end points included OS, ORR, DOR, CBR, patient-reported outcomes, and safety.

Rugo HS, Bardia A, Marmé F, et al. Sacituzumab Govitecan vs Treatment of Physician’s Choice: Efficacy by Trop-2 Expression in the TROPiCS-02 Study of Patients With HR+/HER2– Metastatic Breast Cancer. Abstract presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract GS1-11.

FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. FDA. April 8, 2021. Accessed December 9, 2022. https://bit.ly/3Fd1wbP

Rugo HS, Bardia A, Marme F, et al. Primary results from TROPiCS-02: A randomized phase 3 study of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (Pts) with hormone receptor–positive/HER2-negative (HR+/HER2-) advanced breast cancer. 

. 2022;40(suppl 17):LBA1001. doi:10.1200/JCO.2022.40.17_suppl.LBA1001

Rugo HS, Bardia A, Marme F, et al. Overall survival (OS) results from the phase III TROPiCS-02 study of sacituzumab govitecan (SG) vs treatment of physician's choice (TPC) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC). 

. 2022;33(suppl 7):LBA76. doi:10.1016/annonc/annonc1089

Patients with hormone receptor–positive, HER2-negative metastatic breast cancer derived benefit with sacituzumab govitecan regardless of Trop-2 expression.

Sacituzumab Govitecan Continues to Prolong Survival in Patients With HR+/HER2– Breast Cancer

Data from a short-term follow-up of the POSITIVE (NCT02308085) trial suggests that 

pausing adjuvant endocrine therapy may be safe

 for women with hormone receptor–positive breast cancer who wish to pursue pregnancy, according to Jamie Carroll, APRN, CNP, MSN.

Although a long-term follow-up is ongoing, data presented at the 2022 San Antonio Breast Cancer Symposium showed that at a median follow-up of 41 months, among 497 patients, 74% of women had at least 1 pregnancy—with 70% of the pregnancies occurring within 2 years. Birth defects were low at 2%. Additionally, 64% of women had at least 1 live birth. The 3-year breast cancer recurrence rate among patients who halted therapy was 8.9% (95% CI, 6.3%-11.6%).

“Patients who had 18 months to 30 months of adjuvant endocrine therapy, stopped their endocrine therapy, had a 3-month washout, and then were allowed up to 2 years to attempt pregnancy, conceive, deliver, and breastfeed—which included the 3-month washout,” Jamie Carroll, APRN, CNP, MSN,

Then, if no pregnancy was achieved by a year, they recommended fertility assessment.”

®, Carroll, a nurse practitioner at Mayo Clinic in Rochester, Minnesota, highlighted her interpretation of the trial findings and how this new data will translate to her clinical practice. 

Moving forward, Carroll shared that she is interested in learning whether these results will apply to women who wish to pause therapy multiple times to have more than one child.

“One questions that I have is [whether] we will recommend that they take it for another 18 months and [attempt to] achieve another pregnancy,” Carroll noted. “My outstanding question is: is there safety in pausing it once again?”

 POSITIVE was a pregnancy outcome and safety [study] of interrupting therapy for women with endocrine responsive breast cancer because patients that have estrogen receptor [ER]–positive breast cancer and are of childbearing age want to know if they can interrupt their endocrine therapy to achieve pregnancy. This was a prospective single-arm study to address that question—is it safe from a breast cancer perspective and will [pregnancy] increase their risk of breast cancer relapse?

The study was looking at only women with ER–positive breast cancer, they were premenopausal [younger than] 42 years of age, and they had to have gotten 18 months of adjuvant endocrine therapy, no more than 30 months of endocrine therapy. [Investigators] did allow prior neoadjuvant or adjuvant chemotherapy plus or minus fertility preservation and [patients] couldn’t have had any clinical evidence of recurrence. The primary end point was breast cancer free interval from time of enrollment.

Approximately 43% were in their upper 30s, 75% had no number of births ahead of breast cancer diagnosis, and then almost all were stage I or II breast cancer, stage III was only 6% of patients. They had varying endocrine therapy with or without ovarian function suppression, [selective estrogen receptor modulator] SERM or aromatase inhibitor. Approximately 62% had prior chemotherapy and approximately half and half had mastectomy vs lumpectomy. The outcomes are showing that pausing the endocrine therapy does not impact short-term disease outcomes.

Is pausing therapy something you point women who are receiving adjuvant therapy to and how might you talk about those conversations?

I have this conversation frequently with patients because I have many premenopausal women who have ER-positive breast cancer. I had this conversation today with a 20-something year old woman who is getting her last cycle of neoadjuvant chemotherapy and is already asking, “Can I look at getting pregnant in the future?”

It's a common discussion that we have and it’s helpful to know that the POSITIVE trial did not see that disrupting endocrine therapy impacted disease outcomes. That’s helpful for patients and providers to know that they’re not seeing an increase in recurrence when endocrine therapy is paused to achieve pregnancy.


Partridge A, Niman SM, Ruggeri M, et al. Pregnancy outcome and safety of interrupting therapy for women with endocrine responsIVE breast cancer: primary results from the POSITIVE trial (IBCSG 48-14 / BIG 8-13). Presented at 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX.

Jamie Carroll, APRN, CNP, MSN, weighs in on how findings from the POSITIVE study may change dialogue surrounding pregnancy for women with estrogen receptor–positive breast cancer who wish to pause adjuvant therapy. 

POSITIVE Study Findings Shift Conversations on Pregnancy in ER+ Breast Cancer 

Patients experiencing tamoxifen-related side effects may benefit from cannabidiol (CBD) oil, according to a poster presentation from the 

2022 San Antonio Breast Cancer Symposium.

CBD led to decreases in several tamoxifen-related adverse effects (AEs). Without CBD, the percentage of patients (n = 26) who experienced grade 1 or 2 insomnia was 62% (n = 16) and 38% (n = 10), respectively. With CBD, the rates of grade 1 or 2 insomnia were 73% (n = 19) and 12% (n = 3). Similarly, with for hot flashes, tamoxifen alone induced grade 1 and grade 2 symptoms in 77% (n = 20) and 19% (n = 5) of patients, respectively, whereas the addition of CBD yielded grade 1 and 2 symptoms in 85% (n = 22) and 4% (n = 1) of the population.

Without CBD, the rates of arthralgia were 58% (n = 15) and 38% (n = 10), respectively. Following CBD, these rates were 81% (n = 21) and 12% (n = 3). The rate of grade 1 mood alterations decreased from 73% (n = 19) to 65% (n = 17) following CBD, and the rate of grade 2 mood alterations remained at 4% (n = 1). Similarly, with no CBD, the rate of grade 1 muscle cramps was 27% (n = 7) and the grade 2 rate was 4% (n = 1). Following CBD, no patients reported grade 2 muscle cramps and the rate of grade 1 muscle cramps was 31% (n = 8).

The rate of headache was consistent across the 2 groups: 4 patients (15%) experienced grade 1 headaches both with and without CBD. Vaginal dryness decreased from 2 patients (8%) and 1 (4%) patient with grade 1 or 2 severity without CBD, to 1 patient (4%) with grade 1 severity with CBD. Four patients (15%) and 2 patients (8%) experienced grade 1 amnesia without and without CBD, respectively. Where 2 patients (8%) experienced weight gain with tamoxifen alone, 1 patient (4%) did so with CBD.

Moreover, the mean heath related quality-of-life (HR-QOL) without CBD was 74.3 and the mean after 4 weeks of CBD was 79.0, translating to a 4.7-point increase in HR-QOL (95% CI, 1.8-7.6; 

 = .003). In terms of endocrine symptoms, the mean without CBD was 47.1 and the mean after 4 weeks of CBD was 53.8. In this population, endocrine symptoms improved by 6.7 points (95% CI 

Tamoxifen is often associated with bothersome AEs, which may negatively effect a patient’s QOL, as well as treatment adherence, wrote study authors. Many patients seeking relief from these AEs have fixes their attention to cannabinoids such as cannabidiol (CBD), they continued; however, the effects of CBD on tamoxifen-related AEs have not been investigated. Moreover, because tamoxifen is mainly metabolized through CYP2D6, and CBD is suggested to be an in-vitro inhibitor of CYP2D6, the use of CBD might affect tamoxifen pharmacokinetics.

“The aims of this study were to determine the pharmacokinetic interaction between CBD and tamoxifen, and to subsequently investigate where there is a beneficial influence of CBD on tamoxifen-related [AEs] and [QOL],” Sanne Buijs, MD, of the Department of Medical Oncology, Erasmus MC Cancer Institute, and co-investigators wrote.

To that end, investigators enrolled patients with endoxifen levels of at least 16 nM and at least one tamoxifen-related AE, including hot flashes, arthralgia, mood alterations, and insomnia.

Median patient age was 49.5 years [range, 47-54], the median BMI was 26.1 [range, 24-31], and the median months of tamoxifen use was 13 [range, 5-24]. Thirteen patients (50%) had received local treatment with lumpectomy plus radiotherapy, 4 (15%) had received mastectomy alone, and 9 (35%) had received mastectomy plus radiotherapy. Twenty patients (77%) had undergone neoadjuvant chemotherapy and one patient (4%) had received neoadjuvant anti-HER2 therapy.

Of note, CBD led to toxicities in 38% of patients, all of which were categorizes as grade 1 in accordance with Common Terminology Criteria for Adverse Events guidelines.

With no CBD, 3 patients experienced grade 1 and grade 2 fatigue (12% for both). However, with CBD, 8 patients (31%) experienced grade 1 and 1 patients (4%) experienced grade 2 fatigue. No patients experienced dry mouth or nausea with tamoxifen alone, but these toxicities were reported by 3 (12%) and 2 (8%) of patients receiving CBD.

Study authors acknowledged that 4 weeks of CBD use was a short amount of time for a study, and that a longer study period may yield better insights on CBD and clinically relevant improvements in HR-QOL.

Investigators also noted that the combination of CBD and tamoxifen did lead to a significant decrease in endoxifen plasma concentrations, but this decrease remains within bio-equivalence boundaries and is not considered clinically relevant.

Buijs S, Braal CL, Buck SAJ, et al. CBD-oil: a potential solution in case of severe tamoxifen-related side effects. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. P1-02-08.

Cannabidiol oil may be useful in helping patients with breast cancer manage tamoxifen-related adverse effects. 


Loperamide prophylaxis showed promising results in curbing rates of grade 3 diarrhea for patients with HER2-positive breast cancer who received adjuvant pyrotinib (Irene) plus nab-paclitaxel (Abraxane); however, better antidiarrheal prophylaxis are still needed in this setting, according to a poster presentation from the 

In a cohort of patients receiving loperamide 3 times daily on days 1 through 7 and twice daily for days 8 through 21 with the initiation of adjuvant therapy (cohort A; n = 60), the incidence of any grade diarrhea was 92%. The rate of grade 3 or worse diarrhea was 33%, and none of these cases were categorized as severe by investigators. The median number of grade 3 or worse diarrhea episodes was 1 (IQR, 1-2), and the median time to first grade 3 diarrhea event was 6.5 days (IQR, 1.0-8.3). One patient had to reduce the dosage and 1 patient had to discontinue pyrotinib because of diarrhea.

Among patients who received loperamide 3 times daily on days 1 through 7 and twice daily for days 8 through 42 (cohort B; n = 60), the incidence of any grade diarrhea was 97%. As with the first cohort, the rate of grade 3 or worse diarrhea was also 33%, and none of these cases were categorized as severe by investigators. Similarly, the median number of grade 3 or worse diarrhea episodes was 1 (IQR, 1-1), the median time to first grade 3 diarrhea event was 6 days (IQR, 4.0-10.0), and although 1 patient needed to discontinue treatment because of diarrhea (2%), no dose reductions were reported in response to this adverse effect.

“The effects of both loperamide regimens on antidiarrheal prophylaxis are consistent with that of loperamide prophylaxis in the CONTROL trial (NCT02400476) but with extremely fewer constipation events,” wrote Changjun Wang, MD, associate professor in the Department of Breast Surgery at Peking Union Medical College Hospital, in Beijing, China, and co-investigators, in the poster.

The CONTROL trial was a study assessing antidiarrheal strategies, including dose escalation, in patients with early HER2-positive breast cancer receiving neratinib (Nerlynx), a different pan-HER tyrosine kinase inhibitor (TKI), which was approved in the adjuvant study for this patient population. The study showed that preemptive prophylaxis with loperamide and dose escalation the reduced the rate, severity, and duration of grade 3 diarrhea. However, higher rates of grade 1 or 2 constipation did emerge in this trial.

Pan-HER TKIs are commonly associated with diarrhea, as the study authors explained in the poster; however, there is no consensus on therapeutic or prophylactic strategy of pyrotinib-related diarrhea. 

The ongoing, multicenter single-arm, phase 2 PHAEDRA trial (NCT04659499) is set to evaluate adjuvant pyrotinib plus nab-paclitaxel for patients with low-risk HER2-positive breast cancer. This study included patients with N0/N1mi, HER2-positive invasive breast cancer and primary tumor that were 3 cm or less. These patients received nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for 1 year within 90 days after surgery.

The study presented at the 2022 San Antonio Breast Cancer Symposium showed results from a sub-study of PHEADRA, in which the effect of different prophylactic strategies with loperamide were assessed between 2 cohorts. Patients were randomly assigned to either cohort; the primary end point was the incidence of grade 3 or worse diarrhea and secondary end points include the incidence and severity of diarrhea during the first 2 cycles of adjuvant therapy, the incidence and severity of constipation, as well as the onset time, frequency, and duration of grade 3 diarrhea, as well as the incidence of dose reduction, discontinuation, and hospitalization because of diarrhea, and patients quality of life, as assessed via the Functional Assessment of Cancer Therapy-Breast (FACT-B).

Patients were enrolled between January 2021 and May 20202, and 120 patients were included in the sub-study. In cohort A, the median patients age was 50 years (range, 27-72), 70% of patients had estrogen receptor (ER)-positive and/or progesterone receptors (PgR)-positive disease (n = 42), and 30% had ER-negative and PgR-negative disease (n = 18). Thirty-one patients (52%) had an ECOG performance status of 0 and 29 (48%) had an ECOG performance status of 1. In cohort B, 52 years was the median patient age (range, 29-68); 70% (n = 42) had ER-positive and/or PgR-positive disease, 43% (n = 26) had ER-negative and PgR-negative disease, and 62% (n = 37) and 38% (n =23) of patients had an ECOG performance status of 0 and 1, respectively.

Overall, 3 patients (5%) in each cohort experienced constipation, which were rated as grade 1 or 2. Additionally, 1 patient (2%) in cohort A, and 2 patients in cohort B (3%) needed to reduce their loperamide use because of constipation. No patients discontinued loperamide because of constipation.

Of note, the 2 cohorts demonstrated similar FACT-B total scores during the first 3 months. At months 6 and 9, cohort B demonstrated higher FACT-B total scores.

The poster concluded by noting that long-course and short-course loperamide prophylaxis showed numerically consistent incidence of grade 3 or worse diarrhea, and long-course administration appears to result in a better long-term quality of life.

“Proactive diarrhea management can promote the full-dose and full-course treatment with pyrotinib,” study authors wrote. “It is still necessary to develop more effective antidiarrheal prophylaxis regimens for pan-HER tyrosine kinase inhibitors.”

Wang C, Zhou Y, Lin Y, et al. Antidiarrheal prophylaxis with loperamide for patients with lymph node-negative (N0) or micrometastatic (N1mi) HER2-positive breast cancer who received adjuvant pyrotinib plus nab-paclitaxel: a randomized sub-study of PHAEDRA. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. P1-12-03.

Barcenas CH, Hurvitz SA, Di Palma JA, et al. Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial. 

. 2020;31(9):1223-1230. doi:10.1016/j.annonc.2020.05.012

Loperamide prophylaxis was linked to low rates of grade 3 diarrhea in patients receiving adjuvant pyrotinib, but better antidiarrheal prophylaxis options are still needed in this setting. 

Non-Hispanic Black patients with hormone receptor (HR)–positive/HER2-negative breast cancer were more likely to have worse outcomes vs non-Hispanic White, Asian, and Hispanic patients, even with similar 21-gene recurrence scores, according to an analysis of the phase 3 RxPONDER trial (NCT01272037). The findings were presented at a press conference during the 2022 San Antonio Breast Cancer Symposium.

In RxPonder, investigators evaluated 4048 patients with HR-positive/HER2-negative breast cancer with 1 to 3 positive lymph nodes and a recurrence score of less than or equal to 25 whose race and ethnicity were known. Results showed that non-Hispanic Black patients were found to have a 5-year invasive disease-free survival (iDFS) rate of 87.2% vs 91.5% in non-Hispanic White patients (unadjusted HR, 1.39; 95% CI, 1.01-1.91; 

When conducting a multivariable analysis accounting for recurrence score, treatment arm, menopausal status, age, and grade, non-Hispanic Black patients had a 37% increased risk of invasive cancer than non-Hispanic whites, as well as lower distant relapse-free survival.

Of the race/ethnicities included on the trial, non-Hispanic Black patients had the worst overall iDFS outcomes while Asian patients had the highest (HR, 0.67; 95% CI, 0.45- 1.00; 

“Non-Hispanic Black woman with HR-positive/HER2-negative breast cancer, 1-3 positive lymph nodes, and recurrence score of less than or equal to 25, have worse outcomes compared with non-Hispanic White woman independent of recurrence score, treatment arm, age, and grade,” lead study author, Yara Abdou, MD, said in a presentation of the data. “[However], adjusting for body mass index [BMI] appears to decrease this effect.”

Abdou, a medical oncologist with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina, reported on the RxPonder analysis during the 2022 SABCS.

The randomized phase 3 RxPONDER trial evaluated standard adjuvant endocrine therapy with or without chemotherapy in patients with HR-positive/HER2-negative breast cancer with 1 to 3 lymph nodes.

Investigators evaluated the 21-gene recurrence score, as well as the benefit of adjuvant chemotherapy in these patients, and for a recurrence score of less than or equal to 25. The genomic test measures tumor tissue to predict the risk of breast cancer recurrence, as well as the likelihood of responding to treatment.

Earlier data from the study showed that among premenopausal women with 1 to 3 positive lymph nodes, and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer iDFS and distant relapse–free survival (DRFS) than those who received endocrine-only therapy. Postmenopausal patients with similar characteristics did not benefit from adjuvant chemotherapy.

In the 4048-patient trial, patients were non-Hispanic White (70%), non-Hispanic Black (6.1%), Hispanic (15.1%), Asian (8.0%), or Native American or Pacific Islanders (0.8%).

The median age of patients was 58 years old for non-Hispanic Whites, non-Hispanic Black patients, and Native American or Pacific Islander patients; the median age for Hispanic and Asian patients on the trial was 55 and 50 years, respectively.

Moreover, less non-Hispanic Black patients were pre-menopausal patients (23%) vs Asian patients (58%), for example. There were also no notable differences in tumor size, positive node status, or recurrence score distribution across all racial groups.

Further data showed that non-Hispanic Black patients had a DRFS rate of 90.1% vs 94.7% with non-Hispanic White patients (HR, 1.39; 95% CI, 1.01- 1.91; 

Investigators also evaluated acceptance of treatment assignments by race/ethnicity groups. Data showed that 93% of non-Hispanic Black patients accepted their treatment assignment vs 86% of non-Hispanic Whites accepting their treatment, demonstrating that treatment compliance is less likely attributable to differences in treatment outcomes.

Although recurrence scores were similar across all patient and racial subgroups, data showed that non-Hispanic Black patients had a higher likelihood of presenting with higher grade tumors (18%) vs non-Hispanic White patients (10%). Furthermore, non-Hispanic Black patients had the highest BMI scores across all subgroups.

“Black women have 4% lower incidence [rate], but a 40% higher breast cancer mortality than White women,” Abdou added.

The authors noted that a limitation of the study was the limited number of events that occurred in the non-Hispanic Black patient cohort, regardless of menopausal status. Longer follow-up and additional analyses are needed to confirm the findings.

Abdou Y, Barlow WE, Gralow JR, et al. Race and clinical outcomes in the RxPONDER Trial (SWOG S1007): clinical trial Rx for positive node, endocrine responsive breast cancer. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San San Antonio, TX. Abstract GS1-01.

Kalinsky K, Barlow WE, Gralow JR. 21-gene assay to confirm chemotherapy benefit in node-positive breast cancer. 

. 2021; 385(25):2336-2347. doi:10.1056/NEJMoa2108873

Non-Hispanic Black patients with hormone receptor (HR)–positive/HER2-negative breast cancer were more likely to have worse outcomes vs non-Hispanic White, Asian, and Hispanic patients, even with similar 21-gene recurrence scores.

Black Women With HR+ Breast Cancer Experience Inferior Outcomes, Despite Comparable Recurrence Scores

The dual HER2-blocakde of pertuzumab (Perjeta) and trastuzumab (Herceptin) improved the rate of pathological complete response (pCR) in patients with HER2-positive breast cancer compared with regimens that contain trastuzumab only, according to results of a single-center, real-world analysis from Canada. Moreover, the combination was neutral on drug cost, according to investigators.

Data from 83 patients who received anti-HER2 therapy in the neoadjuvant setting at Jewish General Hospital between 2015 and 2021showed that adding pertuzumab to trastuzumab resulted in a pCR rate at surgery of 62% compared with 27.3% in those treated with trastuzumab alone (

 = .0016), reported Francois Panet, MD, MSc, at the 

For patients with nonmetastatic T2 or node-positive HER2-positive breast cancer, neoadjuvant treatment can allow for less invasive surgery and can select higher-risk patients who fail to achieve a pCR. Standard of care in patients who do not achieve pCR is 14 cycles of adjuvant ado-trastuzumab emtansine (T-DM1), but this treatment comes with significant cost and more adverse effects (AEs) than trastuzumab alone.

The National Comprehensive Cancer Network guidelines have endorsed the use of trastuzumab and pertuzumab combined with chemotherapy in the neoadjuvant setting. Pertuzumab, however, is often not reimbursed depending on the health system.

Patients who don’t achieve a pCR at surgery are eligible for adjuvant T-DM1, which adds toxicities as well as cost to the healthcare system.

“At Jewish General Hospital, pertuzumab was routinely added to standard neoadjuvant therapy after 2019, and this allowed us to compare patients treated before they started using pertuzumab and after,” Panet, a medical oncology fellow at McGill University, Mont-Royal in Quebec, Canada, said.

Thirty-nine patients with localized HER2-positive breast cancer received treatment with dual HER2 blockade and 44 with trastuzumab alone. Tumor stage was T1 or T2 in 68% of the group who received dual HER2 blockade and 73% in those who received trastuzumab alone. Half of patients in the pertuzumab/trastuzumab group were hormone receptor (HR)-positive, vs 66% in the trastuzumab monotherapy group.

The most common neoadjuvant chemotherapy in both time periods was 8 to 12 weeks of anthracycline followed by taxane therapy, 62% in those receiving dual HER2 blockade and 75% in those treated with trastuzumab alone.

“We saw a big increase in pCR, more so in the HR–negative [group] than in the HR–positive patients,” he said, although the increase in pCR rate was observed in both subgroups. In the HR-negative group, the pCR rate was 40% with trastuzumab alone vs 84% with the use of both trastuzumab and pertuzumab (

 = .0098). In the HR-positive patients, the pCR rates were 21% with trastuzumab alone and 40% with dual HER2 blockade (

Neoadjuvant pertuzumab/trastuzumab increased the rate of pathological complete response in patients with HER2-positive breast cancer. 