Primary resistance to CDK4/6 inhibitors in the frontline setting can lead to rapid disease progression and necessitate earlier transition to subsequent therapies in metastatic hormone receptor (HR)–positive breast cancer. Accordingly, the detection of 

mutations through circulating tumor DNA (ctDNA) monitoring may facilitate real-time treatment adaptation in this setting, offering a strategy to identify emerging endocrine resistance and guide the use of oral selective estrogen receptor degraders (SERDs), according to Sara M. Tolaney, MD, MPH.

Topline data from a planned interim analysis of the ongoing phase 3 SERENA-6 trial (NCT04964934), reported in a press release, showed that the study met its primary end point of improved progression-free survival (PFS) with the addition of the oral SERD camizestrant to a standard-of-care (SOC) CDK4/6 inhibitor vs continuation of the frontline aromatase inhibitor (AI) plus CDK4/6 inhibitor in patients with HR-positive/HER2-negative advanced breast cancer harboring an emergent 

 mutation. Notably, all patients in SERENA-6 underwent serial liquid biopsies every few months to monitor for 

“This represents a potential paradigm shift in the way that we’re thinking [about testing for 

 mutations],” Tolaney shared in an interview with 

®. “I’ve never used ctDNA monitoring [of 

 mutation status] to make therapeutic decisions; usually I wait until the time of disease progression. This could be a big step forward.”

In the interview, Tolaney discussed challenges in the frontline management of advanced HR-positive breast cancer, differences in survival outcomes between frontline CDK4/6 inhibitors, and emerging strategies within HR-positive breast cancer, such as triplet regimens or continuing CDK4/6 inhibition post-progression.

Tolaney is chief of the Division of Breast Oncology and the associate director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School in Boston, Massachusetts.

: What are some challenges in the frontline treatment of patients with advanced HR-positive breast cancer?

: We’ve been fortunate to have CDK4/6 inhibitors to treat our patients with metastatic HR-positive breast cancer, and now even with early-stage HR-positive disease. Although some patients experience prolonged benefit from these therapies, there is a smaller subset of patients who may be refractory to these agents.

That is a challenge for us because what we find is that these patients don’t last on therapy for very long in the metastatic setting and are moving on very quickly to subsequent lines of treatment.

Understanding why that is occurring is still something that we don’t really have a good grasp on, and what the optimal way is to overcome that resistance is also not entirely clear.

What are some factors you consider when selecting between available CDK4/6 inhibitors?

We’re fortunate to have choices. Three CDK4/6 inhibitors are approved to treat [patients with] metastatic HR-positive breast cancer: ribociclib [Kisqali], abemaciclib [Verzenio], and palbociclib [Ibrance]. Each of these agents, when added to endocrine therapy, has been shown to essentially double PFS in the metastatic setting. They all offer significant improvements in outcomes.

The challenge is that we have seen some differing data with respect to overall survival [OS]. In the first-line setting, the only CDK4/6 inhibitor to have demonstrated a statistically significant improvement in OS has been ribociclib. For example, in [the phase 3] MONALEESA-2 [trial (NCT01958021)], there was a statistically significant survival benefit with ribociclib. Survival benefit has also been observed with abemaciclib in the second-line setting. Although it was not technically statistically significant in the first-line setting, there is about a 14-month [difference] in median OS between the 2 arms, which is a very clinically meaningful benefit.

In contrast, with palbociclib, no survival benefit has been seen in the metastatic setting—whether in the first-line or second-line setting—nor has there been benefit for palbociclib in the early-stage setting. Something about the data has felt different.

Given the clear survival benefit, the vast majority of us will consider ribociclib when selecting a drug in the first-line setting. That being said, treatment decisions need to be individualized by evaluating potential drug interactions, patient comorbidities, and determining the most appropriate option based on the adverse effect profiles of the drugs.

 mutations earlier in the disease course and how might this approach change the management of metastatic disease?

ESR1 has been an important biomarker for understanding resistance to AI therapy. We know that approximately 30% to 40% of patients receiving an AI in the metastatic setting will develop 

 mutations, and these patients are unlikely to benefit from subsequent AI therapy. Therefore, it is critical to determine whether this mutation is present, as it also helps identify patients who are particularly likely to benefit from oral SERDs.

For example, with elacestrant [Orserdu], we’ve seen that the benefits are far greater than standard endocrine therapy in patients whose tumors harbor 

mutation is present is essential for guiding treatment decisions.

Generally, I will obtain a liquid biopsy, specifically, a ctDNA blood draw, at the time of progression on first-line therapy with endocrine treatment and a CDK4/6 inhibitor. I look for an 

 mutation, but I am also assessing for other biomarkers, such as alterations in the PI3K pathway, which may guide optimal therapeutic selection.

One might ask: why wait until progression to test? Why not assess ctDNA while the patient is still receiving an AI, as this could potentially detect early resistance? Even if imaging doesn’t yet show progression, the presence of an 

mutation could indicate that resistance is developing and disease progression is imminent. This raises the question of whether we should begin monitoring patients with serial liquid biopsies during treatment.

The [phase 3] SERENA-6 study did exactly this in a clever way. Patients receiving an AI plus a CDK4/6 inhibitor received liquid assays every couple of months. If an 

 mutation [emerged], they were randomly assigned to receive either camizestrant while continuing CDK4/6 inhibition, or to continue their AI plus the CDK4/6 inhibitor. A recent press release reported that the study met its primary end point, showing that PFS was longer with camizestrant plus CDK4/6 inhibition compared with continued AI plus CDK4/6 inhibition. These data are expected to be presented at the 2025 ASCO Annual Meeting this year.

How do you approach treatment for patients harboring actionable mutations, and how do they compare with strategies for patients without these resistance mutations?

If a patient has another available target—such as a 

alteration—they may be a candidate for an oral AKT inhibitor like capivasertib [Truqap], which targets that pathway. For example, if a patient has an alteration in the PI3K/AKT/PTEN pathway, I would consider fulvestrant [Faslodex] in combination with capivasertib for that patient.

There are certainly other [options] if a patient does not have an

pathway alteration. [In such cases], I may consider fulvestrant with everolimus [Afinitor]. We know that mTOR inhibition can enhance the efficacy of endocrine therapy, particularly in patients with visceral metastases or more aggressive disease.

Another alternative is the continuation of CDK4/6 inhibition beyond progression. For example, if a patient was on an AI plus a CDK4/6 inhibitor, one might consider switching them to fulvestrant combined with a different CDK4/6 inhibitor. Several trials have studied this [approach], although I would say the data are not yet conclusive.

Data from the phase 3 postMONARCH trial [NCT05169567] suggested that switching to abemaciclib improved PFS. Data from the [phase 2] MAINTAIN trial [NCT02632045] demonstrated that switching the endocrine backbone and continuing with ribociclib could also improve PFS. However, data from the [phase 2] PACE [NCT03147287] and PALMIRA studies [NCT03809988] showed that we could not continue palbociclib [beyond disease progression].

[Based on these data], it seems clear that palbociclib should not be continued after progression. It is probably okay to [consider] abemaciclib post–CDK4/6 inhibitor therapy, although most of the available data [in this setting] are from patients [previously treated with palbociclib]. This is the same for the MAINTAIN study; most of the data are from the post-palbociclib setting. As we start using ribociclib more up front, [the utility of] CDK4/6 switching post-ribociclib [remains uncertain].

Do outcomes with estrogen receptor (ER)–targeted agents differ across patient subsets and mutational profiles in the advanced setting?

There do appear to be fairly consistent data across most of the novel ER-targeting agents indicating greater activity in the 

 wild-type disease. For example, in the [phase 3] EMERALD trial [NCT03778931], elacestrant demonstrated a much larger delta in PFS between treatment arms among patients with 

mutations. Similarly, in the [phase 2] AMEERA-3 trial [NCT04059484], amcenestrant appeared to perform better than standard endocrine therapy in patients with 

We have also seen a press release reporting that vepdegestrant, an oral proteolysis-targeting chimera, showed benefit compared with fulvestrant in patients with 

wild-type disease. The trend does appear to be consistent across trials.

That said, there were interesting findings from AMEERA-3 evaluating combination therapy with amcenestrant and abemaciclib, which demonstrated improved outcomes over amcenestrant alone in an all-comer population. This suggests that when moving toward combination strategies, the predictive value of 

Overall, for most oral antiestrogen monotherapies, the presence of an 

mutation appears to be associated with greater benefit compared with SOC therapies.

What’s next for the treatment of patients with metastatic ER-positive breast cancer, particularly in the first line and post–first-line progression?

It’s hard to keep up. The metastatic ER-positive breast cancer space is evolving [rapidly] and it feels like every few weeks [there’s something new]. Right now, the standard approach is to give endocrine therapy with a CDK4/6 inhibitor in the first line. However, for patients who have a

 mutation, we may be moving toward using a triplet regimen. As seen in SERENA-6, we may also begin monitoring with ctDNA in the frontline setting.

Post-progression, there are a plethora of options, which requires a thorough understanding of the genomic alterations present. There are going to be more and more therapies entering the post–CDK4/6 inhibitor space, and [we’ll likely see] more triplets move into the first-line [setting]. The field continues to change very quickly, which is great for our patients, but it can be challenging for us to keep up. It’s nice, though, to see this level of progress.

Camizestrant demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival in 1st-line advanced HR-positive breast cancer with an emergent ESR1 tumour mutation in SERENA-6 pPhase III trial. News release. AstraZeneca. February 26, 2025. Accessed April 21, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/camizestrant-improved-pfs-in-1l-hr-breast-cancer.html

Articles

Sara M. Tolaney, MD, MPH, discusses the value of incorporating ctDNA monitoring of ESR1 mutations into routine management for HR-positive breast cancer.

Early ESR1 Mutation Detection via ctDNA Monitoring Could Enhance Treatment Adaptation in HR+ Breast Cancer

Dr Tolaney on the Optimal Timing of ESR1 Testing in HR+ Breast Cancer  

"[Data from SERENA-6 could lead to a] paradigm shift in the way that we’re thinking [about testing for 

 mutations]. I’ve never used ctDNA monitoring [of 

 mutation status] to make therapeutic decisions; usually I wait until time of progression. This could be a big step forward."

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology and the associate director of the Susan F. Smith Center for Women’s Cancers and a senior physician at Dana-Farber Cancer Institute; as well as an associate professor of medicine at Harvard Medical School, discussed techniques used to identify 

 mutations in hormone receptor (HR)–positive breast cancer, as well as research that could clarify the utility and optimal timing of 

 mutations have emerged as a clinically relevant biomarker for resistance to aromatase inhibitor (AI) therapy in patients with HR-positive breast cancer, Tolaney began. Approximately 30% to 40% of patients receiving AI therapy in the metastatic setting will develop 

 mutations, which are predictive of poor response to further AI treatment, she reported. The presence of 

 mutations is useful in guiding treatment decisions, including the selection of oral selective estrogen receptor degraders, Tolaney stated. For example, elacestrant (Orsedu) has demonstrated improved efficacy compared with standard endocrine therapies in patients whose tumors harbor 

In clinical practice, circulating tumor DNA (ctDNA) assays are often used at the time of patient progression on first-line endocrine therapy plus a CDK4/6 inhibitor to assess the presence of 

 mutations and other actionable biomarkers, such as alterations in the PI3K pathway, Tolaney continued. However, the traditional approach has been to perform molecular testing only at progression, she noted. This raises the question of whether earlier detection of resistance mechanisms—such as 

 mutations—could inform timely intervention and optimize outcomes, Tolaney said.

The ongoing phase 3 SERENA-6 trial (NCT04964934) was designed to address this concept, Tolaney said. In this study, patients with HR-positive/HER2-negative, 

-mutated advanced breast cancer receiving an AI plus CDK4/6 inhibition underwent serial ctDNA assessments, she detailed. Those who had developed an 

 mutation prior to radiographic or clinical progression were randomly assigned to either continue receiving an AI plus CDK4/6 inhibition or switch to camizestrant plus CDK4/6 inhibition. 

 published in February 2025 reported that the trial met its primary end point, demonstrating improved progression-free survival with the camizestrant-based strategy, Tolaney reported. These findings may represent a paradigm shift, supporting the incorporation of longitudinal ctDNA monitoring into routine management and enabling earlier therapeutic intervention in patients with emerging endocrine resistance, Tolaney concluded.

Videos

Sara M. Tolaney, MD, MPH, discusses the ideal time for patients with HR-positive breast cancer to undergo genetic testing for ESR1 mutations.
 

Dr Tolaney on the Optimal Timing of ESR1 Testing in HR+ Breast Cancer

Although the combination of an aromatase inhibitor (AI) and a CDK4/6 inhibitor remains the standard of care for frontline management of advanced hormone receptor (HR)–positive, HER2-negative breast cancer, an increasing reliance on molecular profiling and the lack of predictive tools to reliably stratify patients by endocrine sensitivity continue to complicate treatment selection and sequencing in the second line and beyond, particularly as more agents become available in later settings, according to Erika P. Hamilton, MD.

“It's exciting to have all these new agents. It’s certainly good for patients, but it also makes things a little bit more complicated.” Hamilton said in an interview with 

. “One of the big unmet medical needs [is] being able to have a good assay that can tell us whether our patient is still endocrine-sensitive.”

In the interview, Hamilton discussed the current first-line arsenal in HR-positive breast cancer and addressed the complexity of second-line treatment after progression on a frontline CDK4/6 inhibitor–based regimen. She also emphasized the growing role of molecular testing and expressed anticipation for upcoming data with the oral selective estrogen receptor degrader (SERD) camizestrant (AZD9833), which may shift practice patterns around testing for 

 mutations in patients still receiving first-line therapies.

Hamilton is the director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute in Nashville, Tennessee.

: What are the current challenges in the frontline management of advanced HR-positive breast cancer?

Things are becoming a little clearer [regarding frontline treatment selection]. We definitely have a standard of care in the first-line setting, which is an AI combined with a CDK4/6 inhibitor. We have 3 choices of CDK4/6 inhibitors, and it's standard to use [a CDK4/6 inhibitor–based] combination in the first line. The one small caveat [applies to] patients whose disease progressed within 12 months of an AI in the adjuvant setting, where we use fulvestrant [Faslodex]. Specifically, for those patients whose disease progressed within 12 months in the adjuvant setting and have a 

 mutation, that's where alpelisib [Piqray] becomes a possibility, which is a [shift] from our standard approach. However, the majority of patients receive an AI [in combination with] a CDK4/6 inhibitor.

Luckily, [CDK4/6 inhibitors] are generally well tolerated. We do see fatigue and neutropenia, but we've become very familiar with neutropenia and are comfortable recognizing that it doesn't translate into febrile neutropenia or illness for our patients. It's exciting to see that with these data, overall survival [OS] is now exceeding 5 years. As we get better agents in the second- and third-line settings and beyond, I anticipate that we will see OS lengthen even further.

What are some factors you consider when selecting a CDK 4/6 inhibitor?

The selection of CDK4/6 inhibitors is a big topic. Several years ago, we were probably almost all using palbociclib [Ibrance]. Despite the fact that progression-free survival [PFS] looks identical across these 3 compounds, with palbociclib [plus letrozole], we did not see a benefit in OS [vs placebo plus letrozole in the phase 3 PALOMA-2 trial (NCT01740427)].

[Instead, we had] much stronger data for ribociclib [Kisqali], as well as abemaciclib [Verzenio], in that space. As a result, many [practitioners] have switched to ribociclib as their CDK4/6 inhibitor of choice in the first-line setting. However, this is not universal, and these agents have different adverse effect [AE] profiles. Palbociclib and ribociclib [are associated with] more severe neutropenia, [whereas] abemaciclib has more gastrointestinal toxicity, and ribociclib also has the caveat of needing to monitor EKGs because of potential QTc prolongation. For patients on a lot of cardiac medications or other medications that can prolong the QTc, ribociclib [may not be] a good choice.

We also need to monitor liver function tests with ribociclib. In general, ribociclib [should be] considered [first], but there are certainly patients with other comorbidities or medications [that influence the selection of] CDK4/6 inhibitors. In reality, all 3 are utilized in the first-line setting.

How do you approach treatment selection after progression on a frontline CDK4/6 inhibitor–based regimen? When would you consider switching to another CDK4/6 inhibitor in that setting?

[The management of] second-line, estrogen receptor [ER]–positive breast cancer has become infinitely more complicated. This is where our mutational profiling is extremely actionable. We have elacestrant [Orserdu] for patients with an 

 mutation. We have alpelisib for patients with a 

 mutation, and for patients displaying a 

 mutation, we have capivasertib [(Truqap) plus fulvestrant]. [There are] a variety of very actionable mutations, and it's very clear that single-agent fulvestrant is just not good enough in a post–CDK4/6 inhibitor world. We have multiple randomized trials showing us that PFS with fulvestrant alone post–CDK4/6 inhibition is less than 2 months, which is clearly not good enough for our patients. We [should be thinking] about either using fulvestrant [in combination] with one of those targeted agents, or perhaps elacestrant [alone].

The other data we’ve gotten more recently for a ‘bland’ mutation profile, where we don’t see one of those 

mutations, is reusing CDK4/6 inhibitors. Specifically, the phase 3 postMONARCH study [NCT05169567] probably [provides] our strongest dataset in this setting [and supports] switching the CDK4/6 inhibitor to abemaciclib, particularly if the patient first received ribociclib or palbociclib. This does [generate] a longer PFS. [Thus,] for the most part, we’re thinking about using combinations in that second-line setting, as long as our patient [experienced] benefit from a CDK4/6 inhibitor in the first line.

When and how often are you conducting molecular testing? More specifically, when are you looking for an 

I'm testing after [progression on] their first-line CDK4/6 inhibitor, [because] that's really where it's actionable. [

 mutations are] not as actionable in the first line because they are exceedingly rare [in that setting], so I'm testing there [after patients receive a CDK4/6 inhibitor].

 is also] a bit less actionable in the later lines. The majority of those patients have [developed] endocrine resistance at that point. We're not necessarily going back to endocrine therapy, but sometimes we can. Honestly, this has become a challenging area because 

mutations are helpful. They're certainly linked to therapeutic benefit and can give us a hint as to whether patients might be a bit more likely to still have endocrine-sensitive tumors.

However, it's not perfect. If we look at the data from the [phase 3] EMERALD trial [NCT03778931], approximately 40% of patients were progressing at their first scan, regardless of which drug they received. Endocrine resistance is a real problem in the post–CDK4/6 inhibitor landscape, and we don't have a great way [to determine] who will get continued benefit from endocrine therapy. That's an unmet clinical need right now.

data from the phase 3 SERENA-6 trial (NCT04964934)

 inform the role of camizestrant in advanced HR-positive breast cancer?

The implications for camizestrant are pretty broad. Recall that we've already seen results from a randomized—although not registrational—trial evaluating fulvestrant vs camizestrant at 2 different doses: 75 mg and 150 mg. That study was positive, [showing that] camizestrant at either dosing schedule [demonstrated superior efficacy vs] fulvestrant. Those trials are ongoing in the metastatic setting, and there are ongoing first-line trials [of camizestrant] in combination with CDK4/6 inhibitors.

The first [phase 3 trial] we're going to see [data read out from] is SERENA-6. SERENA-6 asks an interesting question—one that we haven’t talked a whole lot about in breast oncology before—[about] what I would call the 1.5 line. These are patients who are on first-line therapy with an AI and CDK4/6 inhibitor, and then have the emergence of an 

 mutation in the absence of disease progression. [Altering therapy] is not really second-line therapy because patients haven’t progressed, but they have an 

 mutation. [This] tells us something is changing and they’re likely to progress soon. The trial looked at either continuing the AI and CDK4/6 inhibitor [regimen] or switching to camizestrant [plus] a CDK4/6 inhibitor. [According to a] press release, [the study] was positive for [a PFS improvement when switching to the camizestrant regimen].

There are a couple of implications here. First, this will be the first registrational trial of camizestrant, which is important, even though we know this is a great drug. The other is that it could potentially change our practice pattern around testing for mutations. Minimal residual disease [MRD] has been discussed a lot, but we don’t have any good data for that in breast cancer. Testing for MRD is possible, and it can determine whether somebody is likely to have a poor prognosis; however, we don’t have any information on the back end that anything we do helps that patient. There isn’t utility in testing for MRD, but this could [support testing] for something like an 

 mutation as patients are on first-line therapy. I’m very excited for everyone to see [the full] results [from SERENA-6].

As more novel agents, such as antibody-drug conjugates (ADCs) and oral SERDs, emerge in HR-positive breast cancer, how can assays help determine the appropriate treatment sequence for patients?

It's exciting to have all these new agents. It’s certainly good for patients, but it also makes things a little bit more complicated. We also have to be careful when we talk about combinations of drugs. When we add drugs together, tolerability goes down. Inevitably, there are more AEs when [a patient is] taking multiple medications, so we have to keep that in mind.

From a patient-tolerance perspective, I've touched on one of the big unmet medical needs—being able to have a good assay that can tell us whether our patient is still endocrine-sensitive and signaling through that endocrine axis.

We've certainly seen great data with the ADCs. When we think about moving to chemotherapy for a patient with HR-positive disease, we [should be considering] ADCs now. However, we don’t want to move to ADCs before we've exhausted our endocrine therapy. [An assay could] help us determine who should continue to get further lines of endocrine therapy and who is ready to move to ADCs. Then, some of the novel endocrine backbones, whether we're talking about camizestrant or vepdegestrant [ARV-471], as well as some of the other oral SERDs or complete estrogen receptor antagonists are [coming down] the pipeline.

Slamon DJ, Diéras V, Rugo HS, et al. Overall Survival With Palbociclib Plus Letrozole in Advanced Breast Cancer. 

. 2024;42(9):994-1000. doi:10.1200/JCO.23.00137

Camizestrant demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival in 1st-line advanced HR-positive breast cancer with an emergent ESR1 tumour mutation in SERENA-6 phase III trial. News release. AstraZeneca. February 26, 2025. Accessed April 16, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/camizestrant-improved-pfs-in-1l-hr-breast-cancer.html

Erika P. Hamilton, MD, discusses the current role of CDK4/6 inhibitors and evolving targeted therapies in advanced HR-positive, HER2-negative breast cancer. 

Molecular Profiling, Endocrine Sensitivity Are Key to Managing Later-Line HR+/HER2-Negative Breast Cancer

Erika P. Hamilton, MD, discusses how mutational profiles inform the management of HR-positive breast cancer after progression on a prior CDK4/6 inhibitor.  

Dr Hamilton on Treatment Selection After Progression on Frontline CDK4/6 Inhibition in HR+ Breast Cancer

"[There are] a variety of very actionable mutations [we can target in the second-line setting]. It is very clear is that single-agent fulvestrant is just not good enough in a post-CDK4/6 inhibitor world. We [should be thinking] about either using fulvestrant with one of those targeted agents, or perhaps elacestrant."

Erika P. Hamilton, MD, the director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute, discussed how to approach treatment selection for patients with hormone receptor–positive breast cancer following disease progression on a prior CDK4/6 inhibitor in the first-line setting.

The treatment arsenal for second-line estrogen receptor (ER)–positive, HER2-negative breast cancer has become increasingly complex, largely due to the growing clinical utility of mutational profiling in guiding therapeutic selection, Hamilton began. For patients with 

 mutations, elacestrant (Orserdu)—a targeted oral selective estrogen receptor degrader—is a viable option, she stated. Alpelisib (Piqray) should be considered for patients harboring 

 mutations, and capivasertib (AZD5363) is available for tumors with 

 pathway alterations. These molecularly defined subsets allow for the use of precision therapies that offer superior efficacy over historical endocrine-directed monotherapy, Hamilton asserted.

Data from multiple randomized trials have demonstrated that single-agent fulvestrant (Faslodex) is inadequate in the post-CDK4/6 inhibitor setting, Hamilton reported. As such, treatment strategies for these patients should involve fulvestrant combined with a targeted agent, or substituting fulvestrant with elacestrant for 

For patients without identifiable actionable mutations, treatment rechallenge with CDK4/6 inhibition is emerging as a viable strategy, she noted. Findings from the phase 3 postMONARCH trial (NCT05169567) support the use of abemaciclib (Verzenio) in combination with endocrine therapy in patients who have previously received CDK4/6 inhibition with ribociclib (Kisqali) or palbociclib (Ibrance). This approach has been shown to extend progression-free survival in patients who derived clinical benefit from a first-line CDK4/6 inhibitor, Hamilton stated.

Collectively, these developments underscore the importance of genomic profiling at progression and reinforce the role of combination strategies in the second-line setting for ER-positive disease, Hamilton said. Treatment selection should be guided by prior CDK4/6 inhibitor exposure and mutational status, with a focus on optimizing duration of disease control, she concluded.

Erika P. Hamilton, MD, discusses how mutational profiles inform the management of HR-positive breast cancer after progression on a prior CDK4/6 inhibitor.

Molecular Testing and Evolving Treatment Strategies in HR+/HER2– Advanced Breast Cancer | Supplements and Featured Publications

Early ESR1 Mutation Detection via ctDNA Monitoring Could Enhance Treatment Adaptation in HR+ Breast Cancer

Dr Tolaney on the Optimal Timing of ESR1 Testing in HR+ Breast Cancer

Molecular Profiling, Endocrine Sensitivity Are Key to Managing Later-Line HR+/HER2-Negative Breast Cancer

Dr Hamilton on Treatment Selection After Progression on Frontline CDK4/6 Inhibition in HR+ Breast Cancer