Nobody Has Watched It Happen: What We Really Know About Cancer Cells “Waking Up”
Published: September 17, 2026
Every week, I hear some version of the same fear from women who have been treated for breast cancer. “There could be a cell left in me. If I take estrogen, it will wake up.”
Sometimes it comes up when we talk about testosterone. “But what if some of it converts to estrogen? Could that wake something up?”
And there it is again. The fear that even a single drop of estrogen could bring their cancer back.
Someone she trusts has explained it this way, and that explanation stays with her. Now, even thinking about a hormone that might help her feel better comes with a frightening question: could I be putting myself in danger?
I understand why she is scared. After everything she has been through, she wants to do everything she can to keep it from happening again. But I’m curious by nature. When I hear something stated with that much certainty, I want to understand the evidence behind it.
So I went looking.
What do we actually know about estrogen and dormant cancer cells?
What have researchers demonstrated in a dish or an animal?
What have they established in women?
And how much can any of that tell us about the woman sitting in front of us?
Because “estrogen will wake up your cancer” is a frightening thing to worry about, and women deserve to know what supports it, what remains uncertain, and what that means for their own care.
The picture that stays with her
The explanation sounds simple. A few cancer cells may have been left behind. They are resting somewhere in the body. Estrogen reaches them, and they begin to grow. Treatment blocks that signal and helps prevent the cancer from coming back. It makes sense, right?
But the research describes a more complicated process. Dormancy depends on the cancer cells, the tissue around them, and the signals passing between them. Researchers are still working out why some cells remain quiet for years while others begin growing again. [1]
What resting or “dormant” tumor cells actually means
Some cancer cells can travel away from the original tumor and survive elsewhere without forming a growing, detectable tumor. Researchers call this dormancy. (Chemotherapy does not work well for these cells because it targets rapidly dividing cells, not dormant, slow-growing cells.)
Sometimes an individual cell has stopped dividing. In other cases, a small group of cells stays about the same size because cell growth and cell death balance each other out. So “asleep” is a useful image, but it does not describe everything that may be happening. [1,2]
Think of a seed that has settled into soil. Whether it grows depends on both the seed and its surroundings. Researchers are trying to understand which conditions keep cancer cells quiet and which allow them to grow.
What researchers have seen in a dish
One study caught my attention because it looked beyond the cancer cell itself.
Researchers studied dormant, ER-positive breast cancer cells in the laboratory. Inflammatory signals could make those cells start growing again. They also studied nearby support cells, which help make up the tissue surrounding a tumor cell. [2]
When those support cells were stressed, they released inflammatory signals that encouraged cancer-cell growth. One of the ways the researchers produced that stress was by treating the support cells with fulvestrant, a drug that blocks and degrades estrogen receptors. [2] Another lab study found that taking estrogen away made breast-cancer cells grow faster in a model of bone-marrow blood vessels [3].
That is a finding worth understanding. In this laboratory model, interfering with estrogen signaling in surrounding cells contributed to conditions that favored regrowth. This is one reason we need to study the whole environment around a cancer cell and think carefully about what happens when we block or alter an estrogen signal.
What researchers have seen in animals
In 2014, researchers studied human breast cancer cells in mice. But before we apply the findings to women, we need to understand the mice they used.
These were specially bred NSG mice. They were severely immunocompromised, lacking mature T cells, B cells, and functional natural killer cells (immune cells that fight cancer). Other immune defenses, including macrophage and dendritic-cell function, were also impaired. Their ovaries had also been removed. This was a profoundly immune-deficient animal model.[4]
Researchers injected laboratory-grown human breast cancer cells into these mice. Some hormone-receptor positive cells survived as tiny dormant deposits. When estradiol was later supplied, alone or with progesterone, those deposits could grow into larger metastases.
There was another finding, too. Although the starting cells were estrogen- and progesterone-receptor positive, the resulting metastases contained a mixture of cells, including a subgroup that lacked both receptors. The cells growing elsewhere did not all retain the features of the cells originally injected [4].
So what does this experiment tell us?
Estrogen supported growth from dormancy under those particular conditions. That is a meaningful finding. But the experiment did not test what would happen if the mice had an intact immune system. It did not directly show estrogen waking a dormant cancer cell inside a woman with an intact immune system. And it cannot, by itself, support the idea that even a drop of estrogen will bring her cancer back.
That is the distinction I want women to hear when this research is explained to them.
Other animal studies show how much the immune system can matter, too. In one study, immune cells living in the lungs sent signals that helped keep breast cancer cells dormant. Removing those immune cells, or disrupting the signal the cancer cells received, allowed metastatic growth. [5] Separate work in mice found that natural killer cells helped control breast cancer cells in the bone marrow. [6]
These findings give us several pieces of the picture. They do not establish one universal wake-up switch, but they point toward the importance of immune function in controlling cancer growth.
What researchers have found in women
A small human study offers another useful piece of the picture.
Researchers studied 36 women who had no clinical evidence of breast cancer 7 to 22 years after mastectomy. They detected circulating tumor cells in the blood of 13 of them. [7]
Those women were living without clinically apparent cancer even though tumor cells could still be detected. Finding cells and having a growing, detectable recurrence are different things.
Rare organ-transplant cases offer a different clue. Four organ recipients developed breast cancer traced to the same donor. Because recipients receive medicines that suppress their immune systems, researchers considered loss of immune control a possible explanation for the cancer’s growth. The cases do not isolate a single cause, but they add to the evidence that the immune system and the environment around the cells matter. [6]
What stays with me is the fear women carry.
I hear it constantly. A woman who has been through breast cancer is frightened that even a drop of estrogen could wake something inside her. The explanation she remembers is simple: there may be cells left behind, and estrogen could make them grow.
But the biology we have just walked through is far more complicated m and doesn’t support that theory. Researchers are still trying to understand why breast cancer can return after years, sometimes decades, without any sign of disease. Experimental studies show that immune defenses and the tissue surrounding cancer cells can help determine whether those cells remain quiet or begin growing. Human observations offer clues about these processes, although they cannot tell us exactly what triggered an individual recurrence [6].
Interestingly, often the microscopic residual tumor cells do not always match the original tumor. Researchers have found that cells in blood and bone marrow frequently lack detectable estrogen receptors despite coming from women with estrogen receptor-positive tumors. That finding cannot describe every dormant cell, but it should make us cautious about explaining every remaining cell as though it behaves the same way [8].
And estrogen signaling affects the surrounding tissue, too. In the laboratory study discussed earlier, disrupting that signaling in support cells helped create inflammatory conditions that encouraged cancer-cell regrowth. That does not establish what happens overall in women receiving treatment. It does give us a reason to ask more questions about the environment those cells live in.
I want those questions to be part of the conversation.
What keeps cells dormant? What allows them to escape immune control? How does treatment affect the surrounding tissue? And what does it mean for the woman’s bones, sleep, sexual health, ability to think clearly, and daily life if she decides to block or alter estrogen with endocrine therapy?
This is where I want the conversation to widen.
Estrogen is a hormone the body uses throughout life. Its work extends well beyond the breast and reproductive system. It influences bone, blood vessels, the brain, skin, and other tissues. Those functions belong in any conversation about changing its activity.
The bigger questions are what has changed in the cell’s regulation, which signals are sustaining it, and how its surroundings and the immune system influence its behavior. Then we need to ask how much targeting a particular pathway is expected to help this woman, and what the consequences may be for the rest of her body.
That is the conversation I want women to have.
A woman deserves more than a frightening picture of a cell waiting for a drop of estrogen to initiate regrowth. She deserves an explanation of the evidence, its limits, and what it means for her particular situation.
Want to learn more?
Other articles include: Hormones & Breast Cancer: What’s Fact, What’s Fiction?, The History of Breast Cancer Treatments and the Misguided War on Estrogen, The Truth About Estrogen, Breast Cancer, and Hormone Therapy: What the Latest Research Reveals
Download the Balance App to access Breast Cancer: Your Complete Guide·
Grab my Beginner’s Guide to HRT if you are just starting to sort through the hormone conversation.·
Disclaimer: This article is for educational and informational purposes only and is not intended to replace personalized medical advice or individualized care. It is meant to help you understand your physiology, explore evidence-based options, and make informed choices about your health and wellness. Healthcare should be a partnership, not a permission slip, and proactive care is just as essential as treatment. Use this information to engage in open, collaborative discussions with your provider or to make empowered decisions that align with your own values, goals, and comfort level. You are the ultimate authority on your body.
References
[1] Dowling, R. J. O., et al. (2019). Toronto Workshop on Late Recurrence in Estrogen Receptor-Positive Breast Cancer: Part 2: Approaches to predict and identify late recurrence, research directions. JNCI Cancer Spectrum, 3(4), pkz049. https://doi.org/10.1093/jncics/pkz049
[2] Tivari, S., et al. (2018). Reawakening of dormant estrogen-dependent human breast cancer cells by bone marrow stroma secretory senescence. Cell Communication and Signaling, 16(1), 48. https://doi.org/10.1186/s12964-018-0259-5
[3] Ho Han, H., et al., (2015). Abstract B18: Estrogen deficiency causes reawakening of dormant disseminated breast cancer cells via angiopoietin-1/Tie2 signaling. Mol Cancer Ther 1, 14 (12_Supplement_1): B18. https://doi.org/10.1158/1538-8514.TUMANG15-B18.
[4] Ogba, N., et al. (2014). Luminal breast cancer metastases and tumor arousal from dormancy are promoted by direct actions of estradiol and progesterone on the malignant cells. Breast Cancer Research, 16(6), 489. https://doi.org/10.1186/s13058-014-0489-4
[5] Dalla, E., et al. (2024). Lung-resident alveolar macrophages regulate the timing of breast cancer metastasis. Cell, 187(23), 6631–6648.e20. https://doi.org/10.1016/j.cell.2024.09.016
[6] National Cancer Institute. (2025). Expanding research on dormant cancer cells aims to prevent metastasis. Cancer Currents Blog, National Institutes of Health. https://www.cancer.gov/news-events/cancer-currents-blog/2025/metastasis-dormant-cancer-cells-immune-system
[7] Meng, S., et al. (2004). Circulating tumor cells in patients with breast cancer dormancy. Clinical Cancer Research, 10(24), 8152–8162. https://doi.org/10.1158/1078-0432.CCR-04-1110
[8] Fehm, T., et al. (2008). ER alpha-status of disseminated tumour cells in bone marrow of primary breast cancer patients. Breast Cancer Research, 10(5), R76. https://doi.org/10.1186/bcr2143