Neoadjuvant therapy

Neoadjuvant therapy is a treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given. Examples of neoadjuvant therapy include chemotherapy, radiation therapy, and hormone therapy. Neoadjuvant therapy is a type of induction therapy.

Neoadjuvant chemo might be given to try to shrink the tumor so it can be removed with less extensive surgery. Because of this, neoadjuvant chemo is often used to treat cancers that are too big to be removed by surgery when first diagnosed (called locally advanced cancers). Also, by giving chemo before the tumor is removed, doctors can see how the cancer responds to it. If the first set of chemo drugs doesn’t shrink the tumor, your doctor will know that other drugs are needed. It should also kill any cancer cells that have spread but can’t be seen. Just like adjuvant chemo, neoadjuvant chemo can lower the risk of breast cancer coming back.

Neoadjuvant therapy is considered a potential approach to improve long-term survival, and several studies involving single institutions and national cohorts, as well as data from prospective phase II trials, have revealed a survival benefit following the administration of neoadjuvant therapy ¹. The presumable benefits of neoadjuvant therapy include a decrease in tumor burden, which may result in a higher rate of R0 resection, and facilitation of early treatment for micrometastatic disease, which may be undetectable on preoperative radiological images, but may be then detected in early postoperative stages ². The identification of surrogate markers that predict prognostic significance in the resection after neoadjuvant therapy would be beneficial to discriminate patients who experience an immediate early recurrence after surgery.

If your breast cancer is hormone receptor positive (ER+), you may be offered hormone therapy before your surgery (also known as neoadjuvant hormone therapy). The aim of neoadjuvant hormone therapy is also to shrink your breast cancer prior to surgery and control any cancer in lymph nodes or elsewhere in the body.

Hormone therapy is given as an oral medication (tablet). The most common hormone therapy medications are tamoxifen, letrozole, anastrozole and exemestane. If you are premenopausal, you may also be offered an injection (goserelin) to stop the ovaries from making oestrogen. This may be given alone or in combination with tablet hormone therapy.

You may be offered Herceptin if your cancer is HER2-positive.

What is adjuvant chemotherapy?

Adjuvant (meaning “in addition to”) chemotherapy refers to medicines administered after surgery for the treatment of breast cancer. Adjuvant chemotherapy is designed to prevent recurrence of the disease, particularly distant recurrence. Your doctors may recommend chemotherapy if your breast cancer is invasive, has unfavorable prognostic factors, is a certain size, or has spread to nearby lymph nodes. It also may be recommended if you are relatively young at the time of diagnosis.

Neoadjuvant chemotherapy

Neoadjuvant chemotherapy refers to medicines that are administered before surgery for the treatment of breast cancer. Your doctors may recommend neoadjuvant chemotherapy due to the size of the tumor, since the drugs may shrink the tumor and give you more surgical options.

In some cases, a woman who would have needed a mastectomy due to the large size of her tumor can become a candidate for lumpectomy by shrinking the invasive tumor prior to surgery. Neoadjuvant chemotherapy is also performed for certain types of breast cancer, such as inflammatory breast cancer.

With neoadjuvant chemotherapy, you are likely to be given the same chemotherapy drugs that you would be given if you have chemotherapy after your surgery. The aim of treatment is to shrink the tumor in the breast, along with any other breast cancer cells that may be present elsewhere in the body, by killing those cancers cells.

There are some benefits in having neoadjuvant chemotherapy, but it is not for everyone. You may want to consider your options carefully.

Neoadjuvant chemotherapy may be recommended:

• To reduce the size of your breast cancer (tumor) if it is too big to be removed in an operation
• If you have inflammatory breast cancer
• To reduce the size of the tumor so that you can have breast conserving surgery (lumpectomy) instead of mastectomy
• To reduce the size of the tumor so that a smaller amount of tissue can be removed – this may give you a better cosmetic outcome
• To give you time to have genetic testing if you have a strong family history of breast cancer – you may decide to have a different type of surgery if you are found to have an inherited breast cancer gene mutation
• To delay surgery if you are pregnant so that you can deliver your baby as near to full term as possible (certain breast cancer chemotherapy drugs have been found to be safe in pregnancy)
• To give you time to consider your surgical options, including breast reconstruction

Neoadjuvant treatment for breast cancer

Chemotherapy can be given before surgery (neoadjuvant) or after surgery (adjuvant). In most cases, chemo is most effective when combinations of drugs are used. Today, doctors use many different combinations, and it’s not clear that any single combination is clearly the best.

Adjuvant and neoadjuvant drugs:

• Anthracyclines, such as doxorubicin (Adriamycin) and epirubicin (Ellence)
• Taxanes, such as paclitaxel (Taxol) and docetaxel (Taxotere)
• 5-fluorouracil (5-FU) or capecitabine
• Cyclophosphamide (Cytoxan)
• Carboplatin (Paraplatin)

Most often, combinations of 2 or 3 of these drugs are used.

For women who have a hormone receptor-positive (ER-positive or PR-positive) breast cancer, most doctors will recommend hormone therapy (tamoxifen or an aromatase inhibitor, or one followed by the other) as an adjuvant (additional) treatment, no matter how small the tumor is. Women with tumors larger than 0.5 cm (about ¼ inch) across may be more likely to benefit from it. Hormone therapy is typically given for at least 5 years.

If the tumor is larger than 1 cm (about ½ inch) across, chemo after surgery (adjuvant chemotherapy) is sometimes recommended. A woman’s age when she is diagnosed may help in deciding if chemo should be offered or not. Some doctors may suggest chemo for smaller tumors as well, especially if they have any unfavorable features (a cancer that is growing fast; hormone receptor-negative, HER2-positive; or having a high score on a gene panel such as Oncotype DX).

After surgery, some women with HER2-positive cancers will be treated with trastuzumab (with or without pertuzumab) for up to 1 year.

Many women with HER2-positive cancers will be treated with trastuzumab (with or without pertuzumab) followed by surgery and more trastuzumab (with or without pertuzumab) for up to 1 year. If after neoadjuvant therapy, residual cancer is found during surgery, trastuzumab may be changed to a different drug, called ado-trastuzumab emtansine, which is given every 3 weeks for 13 doses. If hormone receptor-positive cancer is found in the lymph nodes, your doctor might recommend one year of trastuzumab followed by additional treatment with an oral drug called neratinib for 1 year.

Pathologic response

After neoadjuvant therapy, a pathologist will check the breast tissue removed during surgery for a pathologic response.

Pathologic response describes how much of the tumor is left in the breast and lymph nodes after neoadjuvant therapy.

Pathologic complete response

In some cases, neoadjuvant therapy will shrink the tumor so much the pathologist can’t find any remaining cancer. This is called a pathologic complete response (pCR).

A pathologic complete response can give some information about prognosis, but it doesn’t change your treatment plan.

Although a pathologic complete response is encouraging, it doesn’t mean the cancer will never return. And, many people who don’t have a pathologic complete response will still do very well.

Pathologic complete response rates to neoadjuvant chemotherapy are highest among women with tumors that are ³:

• High-grade
• Hormone receptor-negative (estrogen receptor-negative and/or progesterone receptor-negative)
• HER2-positive (when the neoadjuvant treatment plan includes trastuzumab and pertuzumab)

However, neoadjuvant chemotherapy can be effective in treating tumors of any grade and hormone receptor status.

After neoadjuvant therapy ends

To check the response to neoadjuvant therapy, you may have several tests, including a clinical breast exam, a mammogram, a breast MRI and/or a breast ultrasound.

Surgery is then planned much in the same way as if you did not have neoadjuvant therapy.

Sentinel node biopsy and neoadjuvant therapy

A sentinel node biopsy checks for cancer in the lymph nodes in the underarm area (axillary lymph nodes). It’s usually done after neoadjuvant chemotherapy, at the time of your breast surgery.

In rare cases, a sentinel node biopsy may be done before neoadjuvant therapy begins.

References

1. Mokdad AA, Minter RM, Zhu H, Augustine MM, Porembka MR, Wang SC, Yopp AC, Mansour JC, Choti MA, Polanco PM. Neoadjuvant therapy followed by resection versus upfront resection for Resectable pancreatic Cancer: a propensity score matched analysis. J Clin Oncol. 2016.
2. Motoi F, Unno M, Takahashi H, Okada T, Wada K, Sho M, Nagano H, Matsumoto I, Satoi S, Murakami Y, et al. Influence of preoperative anti-cancer therapy on resectability and perioperative outcomes in patients with pancreatic cancer: project study by the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci. 2014;21(2):148–158. doi: 10.1002/jhbp.15
3. Li XB, Krishnamurti U, Bhattarai S, et al. Biomarkers predicting pathologic complete response to neoadjuvant chemotherapy in breast cancer. Am J Clin Pathol. 145(6):871-8, 2016.