CXCR4 Antagonists and Breast Cancer

https://www.practiceupdate.com/c/69235/67/13/?elsc...

{video/interview} Timothy J Pluard MD

"...we saw a significant response rate of about 36% in these heavily pretreated patients and about 60+% clinical benefit in these patients. So, there's a signal there that's obviously a phase I trial with early data, but I think it gives us the groundwork to move forward with additional studies. The FDA has granted fast track designation, so we're moving forward with additional studies."

{poster note: This sounds very promising!}

Surgeon Attitudes Toward the Omission of Axillary Dissection in Early Breast Cancer

https://www.practiceupdate.com/C/70820/56?elsca1=e...

• In this survey of 376 surgeons, 49% would definitely or probably recommend axillary dissection for one sentinel node macrometastasis and 63% would definitely or probably recommend axillary dissection for two sentinel node macrometastases. In multivariable analysis, a lower propensity for axillary dissection was significantly associated with treatment of more breast cancer cases, acceptance of a lumpectomy margin of no ink on tumor, multidisciplinary tumor board participation, and Los Angeles SEER site.
• The potential for overtreatment identified in this study indicates the need for education targeted toward lower-volume breast surgeons.

Clinical trial results of tucatinib with T-DM1 shows promise in treating HER2+ breast cancer

https://www.news-medical.net/news/20180711/Clinica...

Phase 1b clinical trial results published in JAMA Oncology show promise for the combination of tucatinib (formerly ONT-380) with T-DM1 against heavily pretreated HER2-positive breast cancer. Of 57 patients treated, 48 percent responded to the combination, with cancer control of median 8.2 months. Importantly, tucatinib acted against brain metastases stemming from HER2+ breast cancer, a major cause of mortality from the disease.

"One of the best things about this drug is that it combines well with nearly everything. It is so well tolerated that when you test tucatinib in combination with other drugs, it feels like you're just giving the other drug. It's a pill. It works. And it hardly causes side effects. It's really a doctor's dream," says Virginia Borges, MD, MMSc, director of the Breast Cancer Research Program and Young Women's Breast Cancer Translational Program at CU Cancer Center.

.... tucatinib is being evaluated in a number of other trials and with additional partners...

Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer

https://www.practiceupdate.com/c/70229/67/13/?elsc...

• In this phase IB study of 57 patients with metastatic or unresectable locally advanced ERBB2/HER2-positive breast cancer treated previously with trastuzumab and a taxane, the maximum tolerated dosage of tucatinib combined with ado-trastuzumab emtansine was determined to be 300 mg administered orally twice daily; the objective response rate was 48%. Median progression-free survival was 8.2 months.
• Tucatinib in combination with ado-trastuzumab emtansine had acceptable toxicity and showed preliminary antitumor activity among heavily pretreated patients with ERBB2/HER2-positive metastatic breast cancer with and without brain metastases.

Circulating ESR1 Mutations at the End of Aromatase Inhibitor Adjuvant Treatment and After Relapse in Breast Cancer

https://www.practiceupdate.com/c/69780/67/13/?elsc...

• In this retrospective study, plasma samples from 42 patients with metastatic breast cancer who completed at least 2 years of aromatase inhibitor treatment and relapsed were assessed for circulating ESR1 mutations. No ESR1 mutations were detectable at the end of adjuvant therapy; however, 5.4% of patients had a detectable mutation at first relapse, and 33% of patients on first-line metastatic treatment receiving aromatase inhibitor therapy had a detectable circulating mutation at time of progression compared with no patients receiving chemotherapy.
• The authors came to the conclusion that detection of circulating ESR1 mutations at the end of aromatase inhibitor–based adjuvant therapy is not clinically useful.

Generation of HER2-Specific Antibody Immunity During Adjuvant Trastuzumab and Reduced Relapse in Resected HER2 Breast Cancer

https://www.practiceupdate.com/C/69665/56?elsca1=e...

• This study analyzed serum anti-HER2 antibodies from a subset of patients enrolled in the NCCTG trial N9831, which includes arm A, in which trastuzumab was not used. Arms B and C received trastuzumab sequentially or concurrently to chemotherapy, respectively. The mean levels of antibodies increased in the trastuzumab arms but not in the chemotherapy-only arm. The proportion of patients who demonstrated antibodies increased by 4% in arm A and by 43% in arms B and C combined (P = .003). Cox modeling demonstrated that larger increases in antibodies were associated with longer disease-free survival in all patients (HR, 0.23; P = .04).
• The authors suggest that the increased endogenous antibody immunity observed in patients treated with adjuvant combination trastuzumab and chemotherapy is clinically significant in view of its association with improved disease-free survival. The findings may have important implications for predicting treatment outcomes in patients treated with trastuzumab in the adjuvant setting.

Combined Digital Screening Best for Detecting Breast Cancers

https://www.practiceupdate.com/C/71789/56?elsca1=e...

The combination of digital mammography (DM) and digital breast tomosynthesis (DBT) detects 90 percent more breast cancers than digital mammography alone, according to a study published in the August issue of Radiology.

Unmet Need for Clinician Engagement Regarding Financial Toxicity After Diagnosis of Breast Cancer

https://www.practiceupdate.com/C/71677/56?elsca1=e...

• This survey-based study of surgeons, medical oncologists, radiation oncologists, and patients was designed to assess whether growing awareness of financial toxicity related to a cancer diagnosis and treatment has led to increased clinician engagement in the face of their patients' heavy monetary burdens and pressures. Overall, 50.9% of medical oncologists, 15.6% of surgeons, and 43.2% of radiation oncologists reported that someone often or always discusses financial burden with patients. Of women worried about finances, 72.8% reported that physicians and their staff were not helpful. Furthermore, 55.4% of women who desired to talk to providers about the impact of their disease on finances or employment did not report relevant discussion.
• Patients report inadequate engagement with clinicians regarding management of financial toxicity, whereas many providers believe these services are made available to their patients. The authors suggest that curing the disease while bankrupting the patient is untenable.

New strategy may lead to more accurate breast cancer diagnoses

https://www.news-medical.net/news/20180718/New-str...

A study in Molecular Oncology indicates that examining the protein and RNA in leftover materials from routine diagnostic tests for breast cancer may lead to more accurate diagnoses.

Using samples from fine needle aspiration from 25 patients with breast cancer and 33 patients with benign lesions, investigators found that such a strategy could distinguish all cancer patient samples from all benign lesions.

In addition to providing a conclusive diagnosis, the analysis may prove valuable for subtyping of breast cancer, for determining appropriate therapies for individual patients, and for monitoring the course of disease and responses to therapy, all through minimally invasive techniques.

Muddling Through: Thanks for your kind words of encouragement. Glad to know that these are of some help and interest. Thanks to everyone who shares research here! (Marijen, I am particularly concerned about your last post re "step therapy." Given new FDA approved testing tools which indicate which drugs are likely to be effective.... might they require patients to use drugs they know ahead of time are not going to be effective...? Troubling. Reading and following....)