Breast Cancer, Metastatic   

Patient with stage IV ER+PR+Her2- breast cancer progressed after CDK4/6 inhibitor+AI and then on Elacestrant. Guardant 360 showed ESR1 mutation and PI...

Controlled extracranial disease on trastuzumab+pertuzumab for 2 years. Treatment options include Enhertu or WBRT. Not a candidate for SRS or neurosurg...

PFS curves appear similar between the AKT-altered vs overall study population in the trial publication. Is there any additional information available ...

In MONALEESA-2, it appears ~22% of those in the ribcociclib group received a subsequent CDK4/6 inhibitor. What was the rationale and could this have i...

Are there other systemic therapy considerations to help achieve sufficient CNS control?

Role of capivasertib vs SERD? What factors help you decide?

Should these patients have a different threshold for utilizing a CDK4/6 inhibitor in the front line metastatic or as part of adjuvant therapy, or SERD...

Would you start with endocrine therapy + CDK 4/6 inhibitor or a chemotherapy based regimen?

RIGHT Choice trial presented at SABCS 2022

How does this change for patients with elevated bilirubin?

How does data from PADA-1 and EMERALD trials impact your decision-making?  

For example, a patient has had multiple dose reductions for neutropenia and required an admission for infection while on palbociclib. Would you switch...

The patient previously received endocrine therapy alone and in combination with CDK 4/6 inhibitor. She does not have any targetable mutations on NGS. ...

Would you treat with 1st line ET + CDK4/6 inhibitor if the patient is only low or moderately ER positive? 

Are you more worried about QT prolongation in this subset of patients?

Add OFS with endocrine therapy plus Taxane-HP combo? What taxane is preferred? 

Following SRS to the brain lesions, is it safe to closely follow the patient for recurrence?

Would you biopsy a metastatic site? 

Is there absolute LVEF threshold you would not use HER2 targeted therapies?

Are there any circumstances where use of T-DXd would supercede the use of CDK4/6 inhibitors or other non-chemotherapeutic options (PIK3CA etc?)

Is there any data on the efficacy of T-Dxd after progression on sacituzumab govitecan? Does your approach differ by hormone receptor status now that ...

If NGS was positive would you treat with HER2 directed therapy? How, if at all, would you incorporate T-DXd into this treatment paradigm?

In which scenarios would you consider a parp inhibitor as the first line treatment of choice? 

If yes, where in sequence would you use it?

Received neoadjuvant ddAC/T followed by adjuvant capecitabine for residual disease and found to have metastatic pulmonary nodules within months of sur...

Does your approach differ across the HER2 IHC spectrum?

In the DAISY trial, ORR of 30.6% in T-DXd treated patients (n = 38) with HER2-null breast cancer

She had been initially treated with neoadjuvant AC-T followed by BCS and RT with high burden residual disease in the breast and lymph nodes.

How do you compare their efficacy overall?

Would you obtain baseline PFT on all patients or only selected high risk patients? Would you repeat PFTs regularly or only if clinically symptomatic?&...

Given strong TDXd efficacy in these patients is there a role to use it earlier than 2nd line? How does prior Her2-directed and/or taxane therapy...

While rare, these patients were excluded from all frontline CDK4/6 inhibitor trials. Is there any data on the efficacy of ribociclib in the CNS or abi...

Would you change to a different CDK4/6 inhibitor or avoid the entire class of drugs?

Results with fulvestrant and letrozole backbone in MONALEESA and MONARCH trials seem comparable, but PALOMA data is somewhat mixed. How do these trial...

Subgroup analyses in MONALEESA-2 suggest more benefit in de novo treatment naive patients, which is in contrast to MONARCH-3 data presented at ESMO 20...

Patient is young. Bilirubin normalizes when tucatinib is held, but again increases to grade 2 when it is restarted. Evaluation for hemolysis was negat...

For example, if the primary breast tumor was HER2 IHC 1+, but a metastatic site was HER2 IHC 0, would you still recommend using T-DXd? Will you chang...

Is there evidence that T-DXd crosses the blood-brain barrier?

Prior studies have shown that there can be significant variation between grading pathologists as to which samples are defined as HER2 IHC +1 versus HE...

Specifically, how do you consider T-DXd use in setting of other antibody-drug conjugates (e.g. sacituzumab vedotin)? Are there any special considerati...

If a patient has a painful breast lesion in the setting of rapidly progressing systemic disease treated with weekly taxol (60 mg/m2), would you feel c...

For example, are you more likely to incorporate T-DXd earlier in sequence for 2+ vs 1+? Is there any justification to change our approach in HER2-zer...

In patients with prior perioperative immunotherapy with early relapse, would re-introduction of immunotherapy be reasonable with high TMB? 

What were your “top 3” presentations/studies coming out of the meeting this year and how will it impact your own clinical practice? ...

The FDA recently approved trastuzumab deruxtecan (T-DXd) in the second line setting. Given the results of DESTINY-Breast03, what is now the role of TD...

Would you consider definitive local therapy (surgery, radiation?) if she achieved a good response to initial systemic therapy?

Would you include a CDK4/6 inhibitor knowing the patient doesn't meet criteria of monarchE trial but still is Stage IV?

Which regimen is preferred in second line for these patients? What is the efficacy of TDXd vs tucatinib in CNS metastases?    

Although grade 3 toxicity rates were low, ~10.5% experience some degree of ILD, are there strategies to reduce risk before treatment starts? Are ther...

The patient is intolerant to trastuzumab deruxtecan. In which clinical settings would you consider reintroduction of TDM1?

In a patient with a history of VTE (now off anticoagulants), is it safe to administer fulvestrant?

Many of the patients on ASCENT trial were heavily pre-treated and require growth factors. With the day 1,8 treatment cycle, is there a way to minimize...

Given seemingly improved efficacy in ASCENT patients who had less prior treatment, would you consider use after only one prior agent rather than two? ...

Are there specific patient cohorts in whom you will more preferentially use sacituzumab govitecan? Can data from ASCENT be applied to patients with C...

Are there differences in outcome among the BRCA mutated subgroup, or others?

To what degree do you factor in patient preference when choosing among available treatments? Are there features of each regimen that you emphasize in ...

CNS recurrence occurred within two years of prior neoadjuvant therapy

In which situations would you consider this a reasonable treatment option? 

What about a higher penetrance PV such as PALB2? See JCO OGR 8/2021 by @Mark E. Robson discussing management of non-BRCA pathogenic va...

The patient is treatment naïve and asymptomatic. She also has disease in the body (bone and liver metastases). 

The patient initially received definitive therapy with AC-T and RT to the breast as well as RT to a solitary bone lesion. She has been on AI for the l...

The patient has extensive liver metastases and a high bilirubin. She has not received any prior systemic therapy in the metastatic setting. 

Patient was on tamoxifen when progression occurred; unable to tolerate adjuvant AI.

The patient was started on chemoimmunotherapy 3 years ago. Recent scans show small treated brain metastases (s/p RT several years ago) and no disease ...

Patient with T2N1 disease and isolated liver metastases. Axilla and liver completely responded to chemo + IO, but limited residual breast enhancement ...

Do any studies support this rationale? Does the presence of a somatic vs germline BRCA mutation impact your decision?

Patient is on fulvestrant+CDK 4/6 inhibitor and with NED for 5 years. In which cases would you consider stopping CDK 4/6 inhibitor? 

Do you discuss patient visits and associated costs when making this decision?

Do you consider placing an Ommaya for IT chemo with methotrexate or cytarabine? Knowing that leptomeningeal carcinomatosis carries such...

If so, after how many cycles of chemotherapy would you switch?

Patient defers chemotherapy. She is currently on anastrozole/Herceptin and perjeta with a response but it is suboptimal. I would like to add a CDK 4/6...

One such patient progressed through trastuzumab/pertuzumab/letrozole and TDM1 alone.  How would you combine ER+ approaches (eg CDK 4/6 inhibitor ...