Neoadjuvant vs. Adjuvant Chemotherapy in Breast Cancer Treatment Selection

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• Neoadjuvant and Adjuvant Therapy Survival Outcomes
• Advantages of Neoadjuvant Chemotherapy
• Pathologic Complete Response (pCR) Significance
• Neoadjuvant Endocrine Therapy Potential
• Avoiding Overtreatment in Elderly Patients
• Towards a Personalized Treatment Approach
• Full Transcript

Neoadjuvant and Adjuvant Therapy Survival Outcomes

Dr. Marc Lippman, MD, clarifies that randomized clinical trials show no significant survival difference between neoadjuvant and adjuvant chemotherapy for breast cancer. Neoadjuvant therapy is administered before surgery, while adjuvant therapy follows surgical intervention. Dr. Marc Lippman, MD, explains that the choice between these timing strategies does not enormously impact overall patient survival rates. This fundamental equivalence provides oncologists with flexibility in treatment planning. The decision often hinges on other clinical factors beyond mere survival statistics.

Advantages of Neoadjuvant Chemotherapy

Dr. Marc Lippman, MD, outlines several critical advantages of neoadjuvant chemotherapy for breast cancer treatment. This approach effectively downstages larger tumors, making patients eligible for breast-conserving lumpectomy instead of mastectomy. Most patients respond to neoadjuvant chemotherapy, causing tumor shrinkage before surgery. From a research perspective, Dr. Marc Lippman, MD, emphasizes the value of having both pre-treatment and post-treatment tissue samples. This allows researchers to directly observe treatment effects on cancer cells and accelerates the development of new therapeutic approaches.

Pathologic Complete Response (pCR) Significance

Pathologic complete response represents a crucial milestone in breast cancer treatment. Dr. Marc Lippman, MD, describes pCR as the miraculous disappearance of all cancer cells from the breast following neoadjuvant therapy. This achievement varies by disease subtype but serves as a tremendous predictor of long-term survival. Patients who achieve pCR typically require no additional systemic therapy after surgery. Dr. Marc Lippman, MD, notes this outcome is particularly fabulous for patient prognosis and treatment simplification.

Neoadjuvant Endocrine Therapy Potential

Dr. Marc Lippman, MD, discusses the emerging role of neoadjuvant endocrine therapy for breast cancer. While complete responses occur less frequently than with chemotherapy, this may reflect insufficient treatment duration rather than inefficacy. Current clinical trials are exploring extended neoadjuvant endocrine therapy regimens lasting six to eight months. Dr. Lippman awaits these results with tremendous interest. He suggests that longer treatment periods might significantly improve response rates for hormone receptor-positive breast cancers.

Avoiding Overtreatment in Elderly Patients

Dr. Marc Lippman, MD, addresses the critical issue of overtreatment, particularly in elderly breast cancer patients. He references a landmark English study involving women over 80 with ER-positive breast cancer. These patients received only Tamoxifen without surgery or radiation therapy. The majority died from causes other than breast cancer, demonstrating that endocrine therapy alone sufficiently controlled their disease. Dr. Lippman advocates for this conservative approach in infirm elderly patients, noting how easily treatment response can be monitored through physical examination or simple imaging.

Towards a Personalized Treatment Approach

Dr. Marc Lippman, MD, challenges conventional treatment paradigms and advocates for more personalized breast cancer care. He shares insights from early neoadjuvant therapy research at the National Cancer Institute. Their approach involved continuing therapy until achieving best response rather than following fixed-duration regimens. The median number of cycles to best response was five, but many women required 7-10 cycles. Dr. Lippman concludes that the optimal approach may involve tailoring treatment duration to individual patient response rather than adhering to preconceived cookbook regimens.

Full Transcript

Dr. Anton Titov, MD: How to select neoadjuvant and adjuvant chemotherapy and hormone therapy protocols for treating breast cancer? Are protocols the same?

You can use neoadjuvant therapy, endocrine neoadjuvant therapy, chemotherapy, or adjuvant chemotherapy or adjuvant endocrine therapy. So you can do both. Randomized clinical trials have suggested that neoadjuvant therapy and adjuvant therapy makes no difference in survival of patients with breast cancer. So it doesn't matter enormously what you do in terms of survival.

Dr. Marc Lippman, MD: But in the neoadjuvant therapy, you have many advantages. First of all, it's easy for patients with larger tumors to downstage tumors. So a patient might not be suitable for lumpectomy and breast conservation. Almost all patients will respond to neoadjuvant chemotherapy, and most patients will respond to neoadjuvant endocrine therapy, so that tumors will shrink.

It shows you what breast cancer therapy will work. So it can guide breast cancer therapy once the tumors are removed. From a research point of view, we are extremely enthusiastic about neoadjuvant therapy because you have an initial biopsy of breast cancer tumor. And then, when the patient goes to surgery after the neoadjuvant therapy is completed, you can get more breast cancer tissue.

You can see what is the effect your treatment had on breast cancer. And it's a tremendously valid way to develop new breast cancer therapies. There's something called pathologic complete response. And miraculously, depending on the disease subtype, subsets of breast cancer patients will have every last cancer cell disappear from the breast when you give them neoadjuvant therapy. That's fabulous.

Pathologic Complete Response (pCR) is a tremendous predictor of survival. We know that patients who have a pathologic Complete Response don't commonly need additional systemic therapy after the surgery, which is wonderful. So neoadjuvant therapy is very useful for guiding breast cancer therapy.

Dr. Marc Lippman, MD: But there is not a big survival advantage, giving therapy before or after surgery, at this time. Neoadjuvant endocrine therapy doesn't induce complete responses as often, mostly because neoadjuvant therapy probably isn't given for long enough time. And now some wonderful new adjuvant clinical trials are going to go for six or eight months to see the effect of longer-term neoadjuvant endocrine therapies in breast cancer.

I await the results of those clinical trials with tremendous interest. Finally, in the United States, we amazingly over-treat patients. It's just amazing. You see breast cancer patients in their 80s. They're infirm and not well. And doctors are talking about mastectomy and radiation therapy, and all this other treatments.

But there's a lovely study done in England for women over 80 who were diagnosed with breast cancer that was ER-positive. Doctors put them on Tamoxifen, no surgery, no radiation, just a tamoxifen pill. And the majority of those women died of something else. In other words, Tamoxifen for these elderly women with indolent ER-positive breast cancer was enough to control their disease till something else got them.

I think that speaks in favor of not over-treating elderly infirm patients with breast cancer. I mean, that's the mother of all neoadjuvant studies, because you're giving it before any therapy, and you're just not quitting. So it's obvious that endocrine neoadjuvant therapy can be very effective.

Plus, it's child's play to follow a woman to see if you're controlling the cancer in a breast. If she's got a lump, you can feel it. It takes thumb and index finger to tell whether she's doing well or not, right? Or a simple imaging test. So there's no emergency here.

So neoadjuvant therapy in infirm patients with breast cancer could be very attractive, in my mind, but it's not done so much in this country. England has led the way there. No one's tried it yet here.

Well, some years ago, I hate to say how many, we first developed neoadjuvant therapy at the National Cancer Institute, when I ran the breast cancer program there. We didn't know how to do neoadjuvant chemotherapy in breast cancer. Who knew? No one had ever done neoadjuvant therapy in breast cancer before.

So we took women, and we said, we don't know how long to give neoadjuvant endocrine therapy. So we'll just give it until we reach the best response and just keep giving them cycle after cycle. We don't care. And as long as we can measure what's going on, why would we stop, right? As long as the breast cancer tumor is shrinking.

And interestingly, even though neoadjuvant regimens these days are usually four or six cycles of therapy, the median number of cycles to the best response, in our hands was five. It means that half the women took 7-8-9-10 cycles of neoadjuvant hormonal therapy to get to their best response. So that was very, very instructive for breast cancer treatment by endocrine therapy.

So I don't think even the best way to do neoadjuvant therapy for breast cancer had been fully identified. Maybe the best way is to base neoadjuvant therapy on how the patient herself is doing, rather than on some preconceived cookbook regimen boiled for half an hour.