Understanding Breast Cancer Cure and Long-Term Recurrence Risks

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• Five-Year Milestone Myth
• ER-Positive Breast Cancer Reality
• Dormant Cancer Cells in Bone Marrow
• Lifestyle Factors and Recurrence Risk
• Stress Management Therapy Impact
• Extended Endocrine Therapy Rationale
• Full Transcript

Five-Year Milestone Myth

Dr. Marc Lippman, MD, challenges the common cultural belief that being cancer-free for five years equates to a cure. He explains that this five-year benchmark is not a biological certainty but a generalized standard. Different cancers have vastly different timelines for considering a patient cured. For example, testicular cancer may be cured after two years without recurrence. Head and neck cancers often require about three years. Acute leukemia and B-cell lymphomas have their own shorter cure timelines. The five-year rule is a useful but imperfect clinical shorthand.

ER-Positive Breast Cancer Reality

Dr. Marc Lippman, MD, presents a sobering reality for the most common breast cancer subtype. He states that patients with estrogen receptor-positive (ER-positive) breast cancer may never be considered cured. This conclusion is based on studies involving over 100,000 women. The data shows recurrence rates continue in a straight line for 25 years after initial treatment. This pattern holds even after completing five years of standard endocrine therapy. There is no statistical evidence of a cure plateau for this disease. The risk of late recurrence persists for decades.

Dormant Cancer Cells in Bone Marrow

The persistence of cancer cells explains the ongoing recurrence risk. Dr. Lippman reveals that essentially all patients with early-stage ER-positive breast cancer have cancer cells in their bone marrow. These cells can remain viable but dormant for many years. The clinical problem is not about eradicating every last cancer cell. This eradication does not happen with current therapies. Instead, the goal is to manage a state where patients coexist with dormant cells. The critical question is what causes these dormant cells to reactivate years or decades later.

Dr. Marc Lippman, MD, emphasizes this is a key area of his research. He seeks to understand the biology of cancer cell dormancy and reactivation.

Lifestyle Factors and Recurrence Risk

Macro-environmental factors play a crucial role in cancer recurrence. Dr. Lippman identifies several modifiable conditions that increase recurrence risk. Obesity, metabolic syndrome, and diabetes are strongly linked to higher recurrence rates. Psychological factors like depression and undue stress also have a significant impact. These factors can influence recurrence years or even decades after the initial diagnosis. Their effect proves that viable cancer cells remain present in the body. The mystery lies in how these systemic conditions communicate with dormant cancer cells.

Dr. Anton Titov, MD, discusses this with Dr. Lippman. They explore how a cancer cell in the bone marrow "knows" about a patient's diet or stress level.

Stress Management Therapy Impact

Randomized clinical trials provide compelling evidence for non-pharmacological interventions. Dr. Marc Lippman, MD, cites unbelievable results from stress management studies. Women who participated in programs like cognitive behavioral therapy had lower recurrence rates. Just 12 weeks of therapy to reduce distress showed benefits a decade later. This is not hocus pocus but data from rigorous trials. Similarly, women who lost weight after diagnosis also saw a reduction in recurrence risk. Effectively treating diabetes also leads to better outcomes. These interventions offer a powerful means of secondary prevention.

Extended Endocrine Therapy Rationale

The persistent risk of late recurrence informs treatment duration decisions. Dr. Marc Lippman, MD, explains the rationale for continuing endocrine therapy beyond five years. Clinical trials have explored giving aromatase inhibitors for up to ten years. This approach makes perfect biological sense given the ongoing risk. The goal is to suppress the microenvironment that could reactivate dormant cells. Extended therapy is considered assuming the treatment toxicity remains manageable. Thank goodness, the annual recurrence rate is reasonably low. However, the cumulative risk over decades makes long-term suppression a valuable strategy.

Dr. Marc Lippman, MD, provides these critical insights during his conversation with Dr. Anton Titov, MD. They delve into the complexities of achieving a lasting remission in breast cancer.

Full Transcript

Dr. Anton Titov, MD: Now, there's one issue here that you're dancing around. You haven't brought it up, but I want to bring it up. It's extremely important. For cultural reasons that have nothing to do with biology, people in the United States have come to understand: if you're free of disease for five years, all will be well. They've used five years as some sort of line in the sand for being cured of a cancer. And it's a pretty good standard.

For example, for colorectal cancer, if you go five years after your surgery and you haven't recurred, colorectal cancer is not going to recur. Five years is a great number.

Dr. Marc Lippman, MD: But there's nothing set in stone about five years. If you look at the most common cancer in young men, testicular cancer, probably if you go two years and you don't recur, you're cured. Probably three years is more than enough for head and neck cancers, and you're cured. For acute leukemia, probably two or three years is more than enough. For B cell lymphomas, three or four years are probably enough to have cured most patients.

For estrogen receptor-positive breast cancer, ER-positive breast cancer, which is the majority of breast cancers, the answer probably is you are never cured. Let me repeat that: you are never cured.

In studies that have been done involving more than 100,000 women with ER-positive breast cancer, you look at their recurrence rates following the completion of five years of endocrine treatment, surgery, and an endocrine treatment—tamoxifen or an aromatase inhibitor. Those women, for the next quarter of a century (that's how long the studies had been, for the next 25 years), their cancer recurrence rates are a straight line going up. There is no evidence for a cure of estrogen receptor-positive breast cancer.

Now, if you are diagnosed when you are 60, the fact that you might still be at risk of recurrence is a little irrelevant because you get to be 95. You're going to die of something else.

Dr. Marc Lippman, MD: But the point that I'm making is, if you look in the bone marrow of estrogen receptor-positive breast cancer patients who have been, quote, cured of their disease—they had early-stage breast cancer—you look at their bone marrow, essentially all of them have breast cancer cells in their bone marrow.

So the problem of estrogen receptor-positive breast cancer, which is the majority of breast cancer, isn't so much getting out every last cancer cell. It doesn't happen. It is that the woman somehow exists with some viable breast cancer cells in her body, which unfortunately in some women reactivate.

Sometimes people use the word dormancy for these cells, but we know cancer cells are there. We also know that many things in the environment that can occur years after a breast cancer diagnosis can influence whether she recurs or not years later.

If the woman gets obese, if the woman gets metabolic syndrome, if the woman gets diabetes, if the woman gets depression, if the woman is unduly stressed—all of these things conclusively have been shown to increase breast cancer recurrence rates. And the only way you can recur is if there were breast cancer cells present that could recur.

And these things can occur years, decades later. One of the great mysteries—actually one of the areas that I work in—has been to understand how these macro-environmental things, distress, depression, obesity, diabetes, how could they talk to breast cancer?

Dr. Anton Titov, MD: How does the breast cancer cell living in your bone marrow know that you had a bad day?

Dr. Anton Titov, MD: How does the breast cancer cell living in your bone marrow know that you had a pepperoni and cheese pizza instead of the kale salad?

Dr. Marc Lippman, MD: It's a very important question and speaks to other means of preventing breast cancer recurrence because we know it's not hocus pocus. It's randomized trials. We know that women who lose weight have a lower recurrence rate. We know that women whose diabetes is treated have a lower recurrence rate.

We know that some women had stress management in randomized trials. Results are unbelievable, unbelievable. We are certain that women who have stress management following their breast cancer diagnosis have lower cancer recurrence rates than women who don't. That's astounding.

I mean, you need a sense of wonder to say, how could it be that 12 weeks of talking therapy, cognitive behavioral therapy, that reduces distress—which is good for everybody—would everybody benefit from that?

Dr. Anton Titov, MD: How could it be that those women who did this have had less breast cancer ten years later? And the data are compelling.

Dr. Marc Lippman, MD: So these are critical issues in understanding hormone treatment of breast cancer. One of the reasons people have sometimes proposed continuing endocrine therapy beyond five years is that there are clinical trials that have suggested giving aromatase inhibitors for ten years.

And this makes perfect sense, assuming there's no toxicity, because we know that we don't eradicate every last cell for ER-positive breast cancer. There's no evidence for that. Patients continue to relapse, albeit at a reasonably low rate—thank goodness—for decades to follow.