Who this is for
“My breast cancer has spread to my liver and lungs. My doctor says it is incurable. Does that mean chemotherapy is my best option?”
Liver metastases in breast cancer do not automatically mean that chemotherapy is the best first treatment.
If this is you, I want you to know something that surprises many patients—and even some doctors.
One of the biggest changes in breast cancer treatment over the last decade is that chemotherapy is often not the preferred first treatment for patients with hormone receptor-positive, HER2-negative metastatic breast cancer, even when the cancer has spread to organs such as the liver or lungs.
Clinical observation
A lady recently contacted me from overseas for a second opinion.
She had recently been diagnosed with breast cancer.
Her biopsy showed the most common type of breast cancer:
- Strongly oestrogen receptor (ER)-positive
- Strongly progesterone receptor (PR) positive
- HER2 negative
Unfortunately, her scans also showed that the cancer had already spread.
Multiple lymph nodes were enlarged.
The cancer had spread to her liver.
It had also spread to her lungs.
Her doctors had told her that the disease was no longer curable.
Naturally, she assumed chemotherapy would be the next step.
In fact, she almost apologetically asked me,
“Doctor, I know the cancer is everywhere. I suppose chemotherapy is now my only option?”
What surprised me
When I first trained as an oncologist, I would probably have agreed.
The thinking was straightforward.
Large amount of cancer.
Cancer involving important organs.
Need a rapid response.
Give chemotherapy.
The approach sounded logical.
It felt aggressive.
At the time, it seemed like we were doing everything possible.
But oncology has changed enormously over the last ten years.
Today, the evidence tells us something that many patients find difficult to believe.
For most patients with hormone receptor-positive, HER2-negative metastatic breast cancer, endocrine therapy combined with a CDK4/6 inhibitor is usually the preferred first treatment—even when the cancer has spread to the liver or lungs.
Chemotherapy may still be needed when the cancer is causing severe and rapidly worsening organ dysfunction, when the cancer is known to be resistant to endocrine therapy, or when there is another clinical reason that urgent chemotherapy is considered more appropriate.
This approach is supported by major clinical trials and international treatment guidelines.
The biggest misunderstanding about liver metastases in breast cancer
Many patients hear one sentence.
“The cancer has spread to your liver.”
Immediately another sentence follows in their mind.
“I need chemotherapy immediately.”
Those two statements are not the same thing.
This is probably the single biggest misunderstanding I see in women newly diagnosed with stage IV breast cancer.
Liver metastases are not the same as visceral crisis
This distinction is extremely important.
‘Visceral metastases’ means that breast cancer has spread to internal organs such as:
- the liver
- the lungs
However, this does not automatically mean that those organs are failing.
A visceral crisis is different.
It means that the cancer is causing severe and rapidly worsening organ dysfunction. Examples may include:
- rapidly worsening liver function because of extensive liver involvement
- severe breathlessness at rest because of extensive lung involvement
- other immediately life-threatening organ dysfunction caused by the cancer
The presence of liver or lung metastases alone is not enough to diagnose visceral crisis.
Brain metastases and extensive bone marrow involvement are also serious, but they require their own specialised assessment and treatment planning.
The important question is not simply,
“Has the cancer spread to an organ?”
It is:
“Is the cancer causing that organ to fail?”
Why endocrine therapy is often the preferred first treatment
Hormone receptor-positive breast cancer is driven, at least partly, by hormones such as oestrogen.
Endocrine therapy works by blocking this hormonal signal or reducing the amount of oestrogen available to the cancer.
CDK4/6 inhibitors are targeted medicines that help prevent cancer cells from dividing.
When these treatments are combined, they can control hormone receptor-positive, HER2-negative metastatic breast cancer for prolonged periods.
For women who have not gone through menopause, ovarian suppression is usually also required.
These treatments are not free from side effects and require regular monitoring. Depending on the CDK4/6 inhibitor, side effects may include low white blood cell counts, fatigue, diarrhoea and changes in liver blood tests. Some CDK4/6 inhibitors, particularly ribociclib, can also affect the heart rhythm, so regular monitoring is important.
“But doesn’t chemotherapy work faster?”
This is probably the most common question I hear.
It sounds logical.
Big cancer.
Big treatment.
Surely chemotherapy must be faster.
In some situations, chemotherapy can produce a response more quickly. This can be especially important when the cancer is causing severe and rapidly worsening organ dysfunction.
However, when there is no visceral crisis, speed is not the only question we should be asking.
The better question is:
Which treatment is most likely to control the cancer for longer while maintaining the best possible quality of life?
In the RIGHT Choice trial, chemotherapy produced a slightly faster response. However, endocrine therapy combined with ribociclib controlled the cancer for longer and was generally better tolerated and caused fewer severe treatment-related side effects.
Modern endocrine-based treatment can control the cancer extremely well while avoiding many of chemotherapy’s familiar side effects, such as:
- hair loss
- recurrent infections
- numbness in the fingers and toes
- prolonged fatigue
- frequent intravenous treatments
Endocrine therapy and CDK4/6 inhibitors can also cause side effects and require regular monitoring.
However, many patients are able to continue family life, work, travel and social activities for prolonged periods.
For many women, this is a major advantage.
The landmark study that changed practice
One of the studies that significantly influenced modern breast cancer treatment was the phase 2 RIGHT Choice trial.
The study included premenopausal and perimenopausal women with clinically aggressive hormone receptor-positive, HER2-negative advanced breast cancer.
Many had:
- a large amount of cancer
- significant symptoms
- cancer involving internal organs
- rapidly progressing disease
Traditionally, many of these women would have received chemotherapy first.
Researchers compared:
- combination chemotherapy
- endocrine therapy combined with the CDK4/6 inhibitor ribociclib
The results were striking.
The average time before the cancer worsened was approximately:
- 21.8 months with ribociclib and endocrine therapy
- 12.8 months with combination chemotherapy
The chance of the cancer shrinking was similar with both treatments.
Chemotherapy produced a slightly faster response. However, ribociclib and endocrine therapy controlled the cancer for longer and caused fewer severe treatment-related side effects.
In simple terms, chemotherapy worked slightly faster, but endocrine therapy combined with ribociclib provided longer cancer control and was generally better tolerated.
The trial involved younger women who had not completed menopause, so it should not be presented as a trial of every patient with metastatic breast cancer.
However, it reinforced an important principle:
Tumour biology, symptoms and organ function matter—not just how extensive the cancer looks on a scan.
Another surprise: routine breast surgery usually does not help patients live longer
Many women ask me another very understandable question.
“Shouldn’t we remove the breast cancer if it is still there?”
It seems logical.
However, randomised clinical trials have shown that routinely removing the original breast tumour after stage IV breast cancer has already been diagnosed does not usually help patients live longer.
Surgery may still be useful when the breast tumour causes:
- pain
- bleeding
- ulceration
- infection
- other significant local problems
It may also be considered in carefully selected situations after discussion by a multidisciplinary team.
However, surgery should not routinely be performed with the expectation that it will prolong life once metastatic disease is already present.
Modern treatment is a marathon, not a sprint
One of the biggest advances in breast cancer treatment is that we now have multiple highly effective endocrine treatments.
Many women receive several different endocrine-based therapies over many years before chemotherapy becomes necessary.
This approach allows us to preserve quality of life while keeping future treatment options available.
Some patients may receive more than one endocrine-based treatment over time before chemotherapy becomes necessary.
Starting with endocrine-based treatment when appropriate can delay chemotherapy and preserve it as an important option for later.
If the cancer eventually begins to grow, mutation testing may help identify additional targeted treatment options.
What I recommended
After reviewing all of her scans, pathology and clinical information, I explained something she had not previously been told.
Although her cancer had spread to the liver and lungs, there was no evidence that these organs were failing.
She did not have an immediately life-threatening visceral crisis.
That changed everything.
Rather than recommending chemotherapy simply because the disease looked extensive, I recommended endocrine therapy together with a CDK4/6 inhibitor as first-line treatment.
Why?
Because my goal was not simply to shrink the cancer.
My goal was to help her:
- live as long as possible
- maintain an excellent quality of life
- preserve future treatment options
That is exactly what modern oncology tries to achieve.
Key takeaways
- Liver or lung metastases do not automatically mean chemotherapy is required.
Treatment decisions should consider the cancer’s biology, symptoms, rate of growth and effect on organ function. - Endocrine therapy combined with a CDK4/6 inhibitor is usually preferred first for hormone receptor-positive, HER2-negative metastatic breast cancer.
Chemotherapy may be required when the cancer is causing severe organ dysfunction or another clinical reason makes urgent chemotherapy more appropriate. - The strongest-looking treatment is not always the most appropriate treatment.
The goal is to choose the treatment that offers the best balance of cancer control, quality of life and side effects.
The science behind this article
This article is based on international guidance from the American Society of Clinical Oncology and the Advanced Breast Cancer international consensus guidelines, together with major clinical trials of endocrine therapy and CDK4/6 inhibitors.
Every patient’s situation is different. Treatment decisions should be individualised after reviewing the cancer’s biology, symptoms, organ function, previous treatments and the patient’s preferences.
Key evidence
- Lu YS, Mahidin EIBM, Azim H, et al. Final results of RIGHT Choice: ribociclib plus endocrine therapy versus combination chemotherapy in premenopausal women with clinically aggressive hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. J Clin Oncol. 2024;42(23):2812-2821. doi:10.1200/JCO.24.00144
- Burstein HJ, Somerfield MR, Barton DL, et al. Endocrine treatment and targeted therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: ASCO guideline update. J Clin Oncol. 2021;39(35):3959-3977. doi:10.1200/JCO.21.01392
- Cardoso F, Paluch-Shimon S, Schumacher-Wulf E, et al. 6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7). Breast. 2024;76:103756. doi:10.1016/j.breast.2024.103756
- Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med. 2022;386(10):942-950. doi:10.1056/NEJMoa2114663
- Khan SA, Zhao F, Goldstein LJ, et al. Early local therapy for the primary site in de novo stage IV breast cancer: results of a randomized clinical trial (EA2108). J Clin Oncol. 2022;40(9):978-987. doi:10.1200/JCO.21.02098
Frequently asked questions (FAQs)
- My Cancer Has Spread to My Liver. Does That Automatically Mean Chemotherapy?
No. Liver metastases alone do not automatically require chemotherapy. Endocrine therapy plus a CDK4/6 inhibitor is often preferred unless the cancer is causing severe organ dysfunction.
- What Is Endocrine Therapy?
Endocrine therapy blocks or reduces the hormones that help hormone receptor-positive breast cancer grow. It is often combined with a CDK4/6 inhibitor.
- Will I Eventually Need Chemotherapy?
Possibly. Some patients need chemotherapy later, while others remain on endocrine-based treatments for prolonged periods.
- Is Stage IV Breast Cancer Curable?
Stage IV breast cancer is generally not considered curable. However, it is treatable, and some patients live for years with a good quality of life using modern endocrine and targeted treatments.
Dr Dilanka De Silva
MBBS, MRCP(UK), MRCP(UK SCE Oncology), FRACP, PhD
Medical Oncologist & Cancer Genetics Physician
Memorial Sloan Kettering Cancer Center Fellow (New York, USA)