What makes breast cancer come back?

Millions of people live with breast cancer, the most common form of cancer worldwide — and also, in most cases, one of the most treatable. However, even after successful treatment, breast cancer can recur.


How does breast cancer spread, why does it sometimes come back, and can lifestyle changes help improve the prognosis for people with a breast cancer diagnosis? We discuss these and other questions in our monthly podcast.

According to data from the World Health Organization (WHO), in 2020 alone there were 2.3 million womenTrusted Source globally who received a diagnosis of breast cancer. Men can also develop breast cancer.

In the United States, approximately 264,000 womenTrusted Source and 2,400 men receive a breast cancer diagnosis each year, according to the Centers for Disease Control and Prevention (CDC). In the United Kingdom, there are about 55,500 new cases of breast cancer in women, and approximately 370 in men, as per Cancer Research UK data.

Breast cancer is thus easily the most commonly occurringTrusted Source form of cancer, but it is also one of the most treatable. “The average 5-year survival rate for women in the [US] with non-metastatic invasive breast cancer is 90%. The average 10-year survival rate for women with non-metastatic invasive breast cancer is 84%,” states the American Society of Clinical Oncology (ASCO) Foundation.

However, there are many different types of breast cancer, some more aggressive than others, which spread more easily and can be more difficult to treat. But why and how does cancer spread from the initial tumor to other parts of the body?

And why does breast cancer sometimes come back, or recur, in people whose initial breast cancer treatment was successful?

The current installment of our In Conversation podcast discusses these and other questions about breast cancer and recurrence risk. Our guests are Dr. Rachael Natrajan and Dr. Liz O’Riordan.

Dr. Natrajan is head of the functional genomics team in the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research (ICR) in London. She specializes in the study of different breast cancer subtypes through the genetic analysis of cancer tumors, with a view to developing new treatments specific to each of these subtypes.

Dr. O’Riordan was a consultant breast cancer surgeon and is a breast cancer patient and advocate. She is the co-author of The Complete Guide to Breast Cancer: How to Feel Empowered and Take Control, a book that explains the different types of breast cancer treatment, and offers advice on how to cope emotionally, sexually, and physically with a breast cancer diagnosis. Her memoir, Under the Knife: The Rise and Fall of a Female Surgeon, is upcoming.

This feature is based on an edited and shortened record of the discussion featured in our podcast. You can listen to this episode of our podcast in full below or on your preferred platform.

Dr. O’Riordan then went through neoadjuvant chemotherapy, and she also underwent a mastectomy — and this was only the beginning of the lengthy combination of treatments she ultimately underwent.

“Lobular breast cancer is one of the rarer types [of breast cancer] and I think it’s important at this point to emphasize that breast cancer isn’t just one disease. It’s a collection of multiple diseases,” Dr. Natrajan noted.

She also went on to explain what it means to have ER-positive, HER2-negative breast cancer: “[I]t’s positive for the estrogen receptor, which means that the cells and the cancer express estrogen, which means in general, you’d be then eligible for estrogen deprivation therapy. People may have heard of drugs like tamoxifen or aromatase inhibitorsTrusted Source — they’ll work to suppress [the] signaling of estrogen, which […] drives the cells to keep dividing, keep proliferating.”

“HER2 is [a] gene that in some breast cancers is highly expressed,” Dr. Natrajan added. “So the cells have lots of this protein circulating around and that drives how they grow, makes them more aggressive. But now there are therapies that suppress that growth, anti-HER2 therapies, so things like Herceptin.”

But why are some types of breast cancer easier to diagnose than others? We are taught to do thorough breast self-examinations to check for unusual lumps, which can be a sign of cancer. However, lumps do not always appear in breast cancer, explained Dr. Natrajan.

This can make it easier for the signs to slip by unnoticed during self-examinations, and even on mammograms.

“In the vast majority of women and men diagnosed with breast cancer, their cells stick together, as they’re called ductal cancers, whereas like Liz was saying […] she has a lobular breast cancer — that’s where there’s a defect in a protein called E-cadherin. It makes the cells not stick together, they grow in what we call single files — that means they’re less likely to be picked up on normal mammograms because they don’t follow the form of a solid mass.”

Why do dormant cells reawaken?
Researchers are still unsure what stimuli dormant cancer cells respond to that trigger them to reawaken and form new tumors, and this is one of the questions that Dr. Natrajan would like to see an answer to.

Theories about the factors that may facilitate their reawakening range from exposure to stressTrusted Source at the cellular level, the erosion of a kind of collagen “blanket”Trusted Source that surrounds dormant cells, to the protective effect of the microenvironmentTrusted Source of dormant cells, which is made out of healthy cells.

“There [are] theories that there’s a kind of cross-talk [between dormant cancer cells and their microenvironment],” Dr. Natrajan told us.

She noted that such cancer cells “tend to evade the immune system […] by actually changing their genetics, expressing different types of proteins so they become undetected, and then they actually can co-opt other types of immune cells that help them grow.”

“[I]f we can start to predict which cells have particular genomic alterations in them — that may lie in a particular area of the tumor that’s fueled by more food, for instance — then maybe we can start to predict if those cells might escape [from the original tumor, escape treatment].”

– Dr. Rachel Natrajan

Predicting which cancer cells may be able to detach and become dormant may help doctors better address the possibility of cancer recurrence in the future.

Cancer recurrence: Knowledge is power
While researchers work to reveal the intricate mechanics of cancer and tumor growth, the reality remains that cancer can recur — so what can a person do to cope with that knowledge and try to reduce that risk?

“I think it’s important that women know that their breast cancer can come back in the future. It’s a really hard thing to tell a woman, you don’t want to tell them when you’ve removed the cancer… It’s really hard to say, ‘Oh, well done, you’ve got a great result, and did you know it could come back in 2 or 3 years’ time?’,” said Dr. O’Riordan in the podcast.

In her view, it is important for people to have accurate information about the possibility of recurrence, especially so that they are able to make healthy lifestyle choices going forward:

“A lot of us shy away from having those discussions and women don’t realize that [breast cancer] can come back 20 or 30 years down the line. And I think for me, it’s all about helping women reduce the risk of that happening [through lifestyle interventions] like exercising, like cutting down alcohol, like knowing how to check what symptoms to look out for.”

First of all, knowing that there is a risk of recurrence can empower people to address a potential comeback early by seeking medical advice as soon as they notice a potential sign.

According to the research and support charity Breast Cancer Now, such signs could include:

changes to the breast or chest area following breast-conserving surgery or a mastectomy, such as changes in skin texture, nipple inversion, or liquid discharge
persistent pain in the back, hips, or ribs that may get worse during the night
sudden weight loss and appetite loss.

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