Dr. Haythem Y Ali

Breast Cancer: Tailoring Treatment, Maximizing Benefit

As breast cancer care moves toward greater precision, treatment decisions increasingly reflect each patient’s tumor biology, risk of recurrence, and expected benefit from therapy. In this interview with “Hospitals” Magazine, Dr. Haythem Y Ali, a specialist in Internal Medicine and Breast Medical Oncology at Henry Ford Hospital in Detroit, Michigan, explains how advances in surgery, radiotherapy, genomic testing, and targeted therapies are shaping more individualized care. He also discusses when treatment can be safely reduced for selected patients and how multidisciplinary collaboration helps deliver the right treatment at the right intensity for the right duration.

Breast cancer treatment has traditionally been very aggressive. Are we now entering an era where some patients can safely receive less treatment?

As I mentioned, aggressiveness is not the name of the game now. There are many terms like de-escalation and escalation, right-sizing, and intensity optimization. They all mean to convey the same message: right treatment, right dose, right duration for the right patient. I’m partial to the latter description because the first almost feels like we’re withholding therapy, the second is too corporate takeover, but the third is in the Goldilocks zone.

Which patients with early-stage breast cancer may be candidates for treatment de-escalation?

I will use your term, de-escalation, and say that the principle is matching therapy to risk level and the likelihood of responding to a certain therapy. These two pillars of decision-making are designated as the prognostic assessment (how risky the tumor is) and predictive assessment (what is the likelihood a treatment will change the outcome). What you want is to use the available tools to determine if the prognosis is good and if the assessment predicts a low likelihood of benefit. This is the ideal patient for de-escalation or intensity optimization, allowing us to treat with simpler regimens with fewer side effects.

How has breast-conserving surgery evolved, and when can it provide outcomes comparable to mastectomy?

It’s important to state here that since the mid-eighties we have known that breast-conserving therapy is equivalent to mastectomy in terms of survival. So, to counter the premise of the question (I may have misunderstood), this is not a future state we aspire to; it’s actually the current standard of care. I confess that we’ve had a hard time convincing some patients of this fact, especially in the MRI era, which is so sensitive it picks up a lot of benign lesions that look a little more suspicious, causing patient and, to some degree, physician anxiety.

Is sentinel lymph-node biopsy still necessary for every patient with early breast cancer, or can it now be safely omitted in selected cases?

No. In recent years, several studies have identified patients with certain characteristics who do not need any form of axillary assessment except clinical exam and radiology.

How are advances in imaging and tumor biology helping physicians decide how extensive surgery really needs to be?

So, these are two different questions. I think advances in imaging have helped us reduce false-positive and false-negative rates and have reduced the likelihood of missing a tumor due to increased breast density. Advances in digital mammography, tomographic techniques (looking at X-rayed tissue in layers or slices), MRI, and ultrasound have made the screening for and diagnosis of breast cancer more effective.

The understanding of tumor biology has been advancing steadily over the past 3–4 decades and accelerating in the past 20 years. We know a lot more about how the cancer cells tick and, more importantly, that it’s not about the cancer cells alone. It’s a whole ecosystem that involves the cancer cell and how the body reacts to it, and even the type of bacteria that live with us. It’s a war, so everything matters: you, your enemy, the terrain, the weather, the equipment, your allies, etc.

Are there patients today who can safely receive less radiotherapy’ or, in selected situations, avoid it altogether?

Yes, this is definitely the case. Just like we have endeavored to figure out the correct intensity of systemic therapy, we have done so with radiation. We have shortened the time radiation is needed and eliminated the need for it in certain situations, such as women over 70 who have low-risk disease.

How have shorter courses and more targeted forms of radiotherapy changed the patient experience?

The most important thing is that it gave time back to the patient, at no cost to efficacy or safety. It also made radiation more accessible. We tend to think more of our privileged environment, but think about all the people who couldn’t afford coming every day for 6 weeks, or had to travel from a remote site and stay 6 weeks at a hotel just so they could be closer to the radiation site. Or even globally, where patients, if they could afford it, travelled to different countries to get radiation. The effect on the financial burden is tremendous, even though we still have a long way to go before access is more universal.

How do genomic tests and tumor biomarkers help determine whether a patient genuinely needs chemotherapy after surgery?

Genomic testing allows you to understand the inner workings of a tumor, which may look under the microscope like a run-of-the-mill tumor, but you find out when studying the genes that it’s more aggressive. Or vice versa: you may think it’s aggressive, but it’s not. I tell my patients it’s sort of like popping the hood of a car to see if the engine is the factory engine or has been altered. If it has been altered, what capabilities does it have? Then you try to tailor your response based on what you see.

For hormone receptor-positive early breast cancer, how are newer targeted treatments changing the approach for patients at higher risk of recurrence?

Of course, the more choices we have, the better. Newer drugs are designed to help overcome pathways that the cancer cells use to escape the grip of prior types of hormone treatments. Simply put, they overcome resistance mechanisms. These resistance mechanisms are the cancer’s escape routes, so blocking as many of them as possible helps you block the cancer’s escape paths.

How do doctors balance reducing treatment with the risk of undertreating the cancer?

This is the art of medicine. As a physician, you have many tools to help make estimates of risk based on tumor morphologic characteristics (what you see with your eyes), pathologic characteristics (what the pathologist sees under the microscope), and genomic characteristics (what we glean from studying the tumor genetics). This is balanced against the benefits we expect from the drugs and what risks the drugs bring to the table. In addition, patient comorbidity (the types of conditions they suffer from) and, most importantly, the patient’s opinion after presenting your best recommendations balance out the five pillars of oncologic decision-making.

How important is the multidisciplinary breast team in deciding which treatments can safely be reduced or avoided?

Extremely important. This question is like asking how important the Joint Chiefs of Staff are in a military force. Without coordination between the different disciplines, there is no coordinated plan, and the efficacy of each discipline diminishes tremendously.

Looking ahead, could breast cancer treatment become increasingly tailored so that every patient receives only the treatment she needs; and no more than necessary?

Absolutely. The future is right treatment, right amount, right duration. This is the essence of precision medicine, and all oncology, in all its disciplines and subspecialties, is moving towards this goal.