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– Penelope Przekop, 5-Star Career

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From: medscape.com

Women with de novo metastatic breast cancer that is confined to a single distant organ may live longer when they undergo resection of the primary tumor, a large cohort study suggested.

The study, of over 22,000 US women with the diagnosis, found that while local therapies were uncommon, they were associated with longer overall survival: Patients who underwent resection of the primary breast cancer, with or without metastatic-site ablative therapy, survived longer than those who received no local therapy.

Metastatic site ablation on its own, however, showed no survival benefit, according to findings published in JAMA Surgery.

The work “highlights how the story is not over for primary site surgery in the setting of metastatic breast cancer,” said Rita Mukhtar, MD, breast surgeon at the University of California, San Francisco, who was not involved in the study.

About 6% of new breast cancer cases in the US are de novo metastatic breast cancer. Systemic therapies are standard, but some retrospective studies have suggested better survival when women also undergo resection of the primary tumor. Prospective studies, however, have been disappointing.

Many argue that resection of the primary tumor shouldn’t be done unless the goal is local control or palliation of symptoms, Mukhtar told Medscape Medical News.

However, she said, the authors of the new study “have done a lot of work showing that not all patients with stage IV are the same.”

For the study, Jennifer Plichta, MD, of Duke University Medical Center in Durham, North Carolina, and her colleagues identified 22,433 patients in the National Cancer Database who had been diagnosed with de novo metastatic breast cancer confined to a single distant organ (brain, bone, liver, or lung). The median age in the cohort was 61 years, and more than two thirds had bone-only metastases.

All patients received at least one type of systemic therapy. Most (68%) received no local therapy, while roughly 15% underwent surgical resection of the primary tumor, 11% received metastatic-site ablative therapy (surgery or radiation), and 6% received both local therapies.

However, she said, the authors of the new study “have done a lot of work showing that not all patients with stage IV are the same.”

For the study, Jennifer Plichta, MD, of Duke University Medical Center in Durham, North Carolina, and her colleagues identified 22,433 patients in the National Cancer Database who had been diagnosed with de novo metastatic breast cancer confined to a single distant organ (brain, bone, liver, or lung). The median age in the cohort was 61 years, and more than two thirds had bone-only metastases.

All patients received at least one type of systemic therapy. Most (68%) received no local therapy, while roughly 15% underwent surgical resection of the primary tumor, 11% received metastatic-site ablative therapy (surgery or radiation), and 6% received both local therapies.

According to the researchers, the findings are consistent with the hypothesis that primary tumor resection may help slow disease progression, whereas targeting metastatic lesions alone may not be enough. Alternatively, they noted, some patients may have received certain treatments with palliative intent only.

“The main takeaway is that we clearly need more research on local therapies for patients with de novo metastatic breast cancer,” Plichta told Medscape Medical News.

She said that prior trials of local therapy in this patient population have not put enough focus on identifying those most likely to benefit.

“There are currently some prospective studies in the works that will hopefully start to address this question in a more rigorous way,” Plichta said, adding that the current findings support such efforts.

An editorial published with the study was cautiously optimistic.

“While its large cohort design provides valuable insights, the retrospective nature and inherent selection bias — where younger, healthier patients with favorable tumor biology are most likely to receive surgery or ablation — limit causal inference,” wrote Leah Kim, MD, of Yale New Haven Hospital in New Haven, Connecticut, and colleagues.

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– Brittany Burgunder

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An enigmatic type of circulating tumor cell called a dual-positive (DP) cell is associated with shorter survival time in patients with advanced breast cancer, according to a study led by investigators at Weill Cornell Medicine and NewYork-Presbyterian. The findings highlight the potential importance of these under-studied cells in breast cancer progression.

Circulating tumors cells are breakaway tumor cells that can seed secondary tumors (metastases) and are commonly detected in the blood of patients with cancer. Dual-positive cells are circulating cells that bear both tumor-cell and immune-cell markers, and are thought to be hybrid cells resulting from rare fusions of tumor cells with immune cells. Recent studies have linked DP cells’ presence in patients’ blood to worse outcomes in melanoma and pancreatic cancer.

In the new study, published March 11 in Science Translational Medicine, the researchers linked DP cells to shorter survival times in patients with advanced breast cancer, especially the aggressive “triple-negative” breast cancer subtype. The team also showed with animal models that DP cells can seed breast cancer metastases.

“A better understanding of the role of these unusual cells in triple-negative breast cancer might help us devise better treatments and methods for predicting and monitoring treatment responses,” said study co-first author Dr. Carolina Reduzzi, assistant professor of cancer biology research in medicine at Weill Cornell Medicine.

Dr. Eleonora Nicolò, instructor of cancer research in medicine at Weill Cornell Medicine is the other co-first author of the study. Drs. Reduzzi and Nicolò are members of the laboratory of study senior author Dr. Massimo Cristofanilli, professor of medicine in the Division of Hematology and Medical Oncology at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.

The team initially analyzed blood samples from 340 women with advanced breast cancer who had agreed to participate in the research study when it began at Northwestern University, where Dr. Cristofanilli was originally located. DP cells tended to be less numerous than ordinary circulating tumor cells, which are a known risk factor for metastasis and shorter survival. However, the researchers identified at least one DP cell in 152 (44.7%) of the women. Patients with three or more detected DPs had median survival times of just 23.5 months, compared to 33.6 months for patients with less than 3 detected DP cells. The association between more than 3 DP cells and shorter median survival was validated in an additional group of 51 patients with advanced breast cancer who agreed to participate in the study at Dr. Cristofanilli’s clinic at NewYork-Presbyerian/Weill Cornell Medical Center.

Comparisons of different breast cancer subtypes indicated that the shorter-survival risk from DP cells was concentrated mainly among patients with triple-negative breast cancer, a subtype in which tumor cells lack the three most common breast tumor markers: estrogen, progesterone and HER2 receptors.

Supporting the hypothesis that DP cells originate from tumor-cell/macrophage fusions, the researchers found that 60% of analyzed DP cells from patients bore a standard macrophage marker. Moreover, the team were able to detect DP cells in breast cancer mouse models only when the mice had intact immune systems.

About 29% of patient DP cells had genetic abnormalities called copy number alterations, which are commonly found in tumors. Although patients’ ordinary circulating tumor cells were more likely to show such abnormalities, DP cells seemed fully capable of seeding metastases in animal models.

The findings underscored the relevance of DP cells in breast cancer and the importance of studying them further. The team is currently conducting a comprehensive characterization of DP cells’ gene expression patterns, which should better define their cellular origins.

“Our current therapies target ordinary cancer cells, but DP cells have a different biology,” said Dr.Cristofanilli, who is also the scientific director and head of the Liquid Biopsy Platform at the Englander Institute for Precision Medicine and the associate director of precision oncology at the Sandra and Edward Meyer Cancer Center. “We need to understand that better if we’re going to target them effectively.”

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– Ashish Kumar, Indelible Journey: Real Life In The Contemporary World

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– Anastasia Petrenko, Be Your Own Guru: 34 Essays on Figuring Out Life

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From: medicalxpress.com

A new study led by researchers at Adelaide University and published in Science Advances reveals why some cancers can grow and survive in the body, while others cannot. It turns out that intense mechanical pressure experienced by early cancer cells as they grow cramped in a restricted space can benefit some cancer cells, rather than impede growth, as might be expected. Scientists found that early breast cancer cells used this “squeeze” to their advantage.

How breast cancer cells sense pressure

Lead researcher, Professor Michael Samuel from Adelaide University’s Center for Cancer Biology and the Basil Hetzel Institute, said these breast cancer cells hijack a specific sensor—one that our bodies normally use to perceive touch—and use it to multiply rapidly and help them migrate away from the primary tumor.

“This process leaves a lasting ‘mechanical memory’ in breast cancer cells, continuing to promote aggressive behavior long after the pressure itself has been relieved,” Professor Samuel said.

“Solid tumors experience intense physical pressure at early stages of the disease, as cancer cells multiply within space-restricted tissues, such as the milk ducts of the breast. Until now, it has been unclear how cancer cells sense this pressure and whether it influences how the disease progresses.

“We tend to think about cancer as a genetic disease, but this work shows that physical forces inside tumors are just as important as cancer-causing genetic changes.”

The PIEZO1 pathway and tumor growth

The researchers found that cancer cells detect pressure through a molecule called PIEZO1, a channel that connects the inside of a cell with the outside environment. When activated by pressure, PIEZO1 allows calcium ions to flow into the cell, triggering a series of signals including the Rho-ROCK pathway—a key regulator of cell movement, shape and growth.

The team showed that brief exposure to mechanical pressure, applied by compressing cancer tissue, was enough to significantly increase tumor growth. In laboratory models of breast cancer, tumors that had been mechanically compressed grew larger and the cancer cells within them divided more rapidly than uncompressed tumors.

Beyond stimulating growth, compression was also found to push cancer cells toward a more aggressive, invasive state through a process known as epithelial-mesenchymal transition. However, when PIEZO1 or the Rho-ROCK pathway had been blocked using appropriate drugs, compression failed to drive cancer aggressiveness, clearly establishing their importance to this process.

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– Lucy Gilmore, The Lonely Hearts Book Club

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From: medicalxpress.com

The alternative medicine industry is expanding rapidly, fueled in large part by the surge of health-related content on social media. This growing trend has become an increasing concern for oncology practitioners and patients, as it can affect treatment decisions and trust in evidence-based care. The worry isn’t unfounded, as a recent study involving patients with breast cancer found that women who chose complementary and alternative medicine (CAM) instead of traditional cancer therapies had a higher risk of dying.

The researchers analyzed data of over 2 million breast cancer patients from a nationwide database. While those who chose CAM alone were very rare, those who did opt for it were about four times more likely to die than those who received conventional cancer treatments. Their survival chances were very similar to those of those who refused any form of treatment. The findings are published in JAMA Network Open.

A risky alternative path

After lung cancer, the second most diagnosed cancer among women is breast cancer. It is also the second highest in cancer-related deaths. Mammography screening, over the past few decades, has lowered breast-cancer deaths by about 20–30% because it helps detect cancer at an earlier stage, when cancer is less aggressive and easier to treat.

We have also seen rapid advancements in cancer treatments. Targeted therapies, such as drugs that act on hormone-sensitive breast cancer and treatments that target the HER2 protein, a protein that controls cell growth and division and can drive more aggressive tumor growth when overproduced, have significantly improved care. Together with many other therapies, these advances have helped lower the chances of cancer returning and increased the long-term survival rate.

Choosing CAM despite these medical advancements is not a new phenomenon, but its use is steadily increasing. More patients are turning to approaches such as acupuncture, dietary supplements, and mind-body practices.

As more patients turn to CAM, it becomes important to understand how these choices might affect survival in breast cancer.

This study set out to explore the question by comparing survival among patients who use conventional therapies vs. CAM. It is also the first study to closely examine outcomes in people who combined CAM with traditional treatments.

To get a clearer overall view of the trend, the team used the massive U.S. National Cancer Database (NCDB), which is a collection of records that captures about 70% of all new cancer cases in the country. They looked at the diagnosis data of women with breast cancer between 2011 and 2021.

The patients were divided into four groups based on their treatment choices: traditional therapies only, CAM only, combination treatment, and no treatment.

Less than 0.1% of the patients went for exclusively CAM, but it is associated with much lower five-year survival, about 60.1% compared with 85.4% for those receiving traditional treatment. Even combining CAM with standard therapy is linked to higher mortality, as women in this group were more likely to skip or refuse essential medical treatments like radiation or hormone therapy.

The researchers believe that the low reported use of CAM or combined therapy may partly reflect patients’ hesitation to discuss alternative approaches with their oncologists. Given the survival risks associated with opting for the alternative route, there is a clear need for open communication between patients and clinicians to ensure they are effectively counseled on the evidence, or lack thereof, for CAM treatments.

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