New Trends in Pre-Surgery Treatments for Breast Cancer


Non-metastatic breast cancers are most often treated with surgery, but if the tumors are fairly large, or involve nearby lymph nodes, neoadjuvant (pre-operative) treatments with chemotherapy (NAC) are done first. NAC often reduces the tumor size and kills cancer cells in lymph nodes, if present, prior to surgery, improving the outcome. The best possible result of neoadjuvant treatment is pCR (pathologic compete response), when the tumor is no longer visible in imaging studies. Here, I review the new directions in which neoadjuvant treatments are evolving.

Today, treatments for metastatic breast cancers are tailored for specific subtypes. Starting with the introduction of the drug trastuzumab (Herceptin) for HER2-positive cancers, new, more specific treatment options were eventually developed and approved for other types as well. Estrogen deprivation endocrine therapies, lately prescribed in combination with CDK4/6 inhibitors, are used in estrogen receptor (ER)-positive cancers. Triple negative cancers (TNBC) are still treated mostly with chemotherapy, but immune checkpoint drugs and PARP inhibitors are explored in clinical trials, with some successes reported.

However, neoadjuvant treatments (except for HER2+ cancers) remain largely limited to chemotherapy regimens. This is starting to change now, with new approaches tailored to the cancer type being investigated in clinical trials.

In this regard, it is important to mention the I-SPY2 trial, NCT01042379, which started in 2010 and is for women with stage II-III breast cancer. It offers about a dozen drugs that are chosen based on particular features of the newly diagnosed cancers. This trial has a unique design and has produced some important results. Additional treatments and trials for various types of breast cancer are discussed below. Continue reading…


Hormonal Therapy Effectively Added to Dual HER2-Blockade in Phase II PERTAIN Study

Excerpt:

“The addition of an aromatase inhibitor (AI) to pertuzumab (Perjeta) and trastuzumab (Herceptin) improved progression-free survival (PFS) by 3.09 months, when compared with trastuzumab plus an AI, according to findings from the phase II PERTAIN trial presented at the 2016 San Antonio Breast Cancer Symposium.

“In the ongoing, open-label study, the median PFS was 18.89 months with the pertuzumab combination compared with 15.80 months for trastuzumab and an AI alone. Furthermore, there was a 35% reduction in the risk of progression or death with the addition of pertuzumab (HR, 0.65; 95% CI, 0.48-0.89; P = .007).”

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Mutation Status May Guide Endocrine Therapy for Advanced Breast Cancer

Excerpt:

“Plasma analysis of ESR1 mutations may aid in the identification of appropriate endocrine therapy for patients with advanced breast cancer who progress after treatment with aromatase inhibitors, according to study results published in Journal of Clinical Oncology.

“ ‘Although diverse mechanisms of resistance to endocrine therapy have been described, recent evidence identified mutations in the ER gene (ESR1),’ Nicholas C. Turner, MA, MRCP, PhD, consultant medical oncologist at The Royal Marsden NHS Foundation Trust and team leader at the Breakthrough Breast Cancer Research Centre at Institute for Cancer Research, London, and colleagues wrote. ‘ESR1 mutations occur rarely in primary breast cancer, but have a high prevalence in advanced breast cancers previously treated with aromatase inhibitors, implying evolution through selective treatment pressure.’ ”

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Radiotherapy Halves Deaths From Prostate Cancer 15 Years After Diagnosis

Excerpt:

“A longitudinal Nordic study, comparing the results of hormone (antiandrogen) therapy with or without the addition of local radiotherapy, shows that a combination of treatments halves the risk of death from prostate cancer 15 years after diagnosis. This according to a follow-up study recently published in the journal European Urology.

” ‘Before the turn of the century, it was tradition to castrate men with high-risk or aggressive local  with no signs of spreading, as the disease at that point was thought to be incurable,’ says Anders Widmark, senior physician and professor at Umeå University, who led the study.”

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No Increased Risk of Fatal CV Events for Breast Cancer Patients on Newer Hormone Therapy

Excerpt:

“In a new study from Kaiser Permanente, researchers found the use of aromatase inhibitors, hormone-therapy drugs used to treat patients with breast cancer, was not associated with an increased risk of fatal cardiovascular events, including heart attacks or stroke, compared with tamoxifen, another commonly prescribed anti-cancer drug that works on hormones and which has been associated with a serious risk of stroke.

“While women taking aromatose inhibitors did not have an increased risk of death from heart attacks or stroke, the study, published today in JAMA Oncology, found that those who only used aromatase inhibitors or used the drugs after tamoxifen treatment had a 26 to 29 percent higher risk of less serious cardiovascular events, such as abnormal heart beat and pericarditis (a swelling and irritation of the thin membrane surrounding the heart), compared with those who only used tamoxifen.”

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Hormone Therapy for Prostate Cancer Tied to Depression

Excerpt:

“Hormone therapy for prostate cancer may increase the risk for depression, a new analysis has found.

“Hormone therapy, or androgen deprivation therapy, a widely used prostate cancer treatment, aims to reduce levels of testosterone and other male hormones, which helps limit the spread of prostate cancer cells.

“From 1992 to 2006, researchers studied 78,552 prostate cancer patients older than 65, of whom 33,382 had hormone therapy.”

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Intermittent Hormonal Therapy Proves to be Viable in Prostate Cancer

“With no significant difference between intermittent and continuous androgen-deprivation therapy, patients with prostate cancer may experience an improvement in their quality of life with the former.

“Androgen-deprivation therapy may be an effective treatment in prostate cancer, though its side effects may result in a loss of quality of life for patients. Allowing low-risk patients to take breaks between treatments—a practice known as intermittent hormonal therapy, or a ‘hormone holiday’—may combat these challenges without impacting survival.

” ‘Intermittent hormonal therapy has been growing in popularity over the years. Patients who receive hormone therapy often have side effects, and giving them so-called “hormone holidays” may improve quality of life. Over the years, there has really been a lot of trials and experimental work that laid the groundwork for this going back 20 years,’ said Leonard G. Gomella, MD, in an interview with Targeted Oncology.”


“Hormone Holiday” Can Improve QoL for Select Patients With Prostate Cancer

“Androgen-deprivation therapy, while an effective treatment for prostate cancer, can result in side effects and a reduced quality of life. Allowing low-risk patients to take breaks between treatments—a practice known as intermittent hormonal therapy, or a ‘hormone holiday’—may combat these challenges without impacting survival.

“A recent systematic review and meta-analysis conducted by JAMA Oncology found no significant difference between intermittent and continuous therapy for overall survival (HR, 1.02; 95% CI, 0.93-1.11; 8 trials, 5352 patients), cancer-specific survival (HR, 1.02; 95% CI, 0.87-1.19; 5 trials, 3613 patients), and progression-free survival (HR, 0.94; 95% CI, 0.84-1.05; 4 trials, 1774 patients).”


Early Chemotherapy Improves Survival for Men with Prostate Cancer

“Two papers from UCL show that having early chemotherapy improves survival for men with prostate cancer. The papers, published in the Lancet and Lancet Oncology, report the results from the STAMPEDE clinical trial and a meta-analysis.

“Both papers looked at the use of a chemotherapy drug called docetaxel. Docetaxel is already used for men with prostate cancer once hormone therapy has stopped working. In STAMPEDE and the meta-analysis, the researchers looked at using it earlier, when men are starting long-term hormone therapy. Both studies found that adding docetaxel improved survival for these men.

“The studies also looked at whether the drug zoledronic acid improves survival. Zoledronic acid is used to reduce the risk of bone problems in men whose cancer has spread to their bones, and whose hormone therapy has stopped working. The new studies looked at using it earlier, when men are starting long-term hormone therapy. Both studies found that adding zoledronic acid did not improve survival for these men.”