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Breast cancer: first the drugs, then the surgery

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“Remove it as soon as possible”. This is what is often thought in the days following the diagnosis of breast cancer. Weed out the “intruder” so as not to give it time to grow and spread. So many patients turn to the surgeon who can operate them faster. But resorting directly to surgery is not always the right way.

Today we know, in fact, that in women with triple-negative or Her2-positive breast cancer larger than 1-2 centimeters, the first treatment should be pharmacological. Especially now that new treatments are available, such as immunotherapy and targeted drugs, as we tell in the latest newsletter of Breast Health. But let’s go in order.

Many types of cancer

Breast cancer affects about 55,000 women in Italy every year. Of these, it is estimated that over 8 thousand (15%, more or less) have a triple negative tumor, while about another 11 thousand (20%) have Her2-positive cancer. What do these names mean?

Most cancers grow stimulated by female hormones because they have receptors that, like antennae, pick up estrogen and / or progesterone (these tumors are called luminal). Her2-positive tumors, on the other hand, have a large number of HER2 receptors, capable of picking up a protein called human epidermal growth factor (there are cases in which the tumors are both luminal and Her2-positive).

Therapies that target these receptors have been developed for these two subtypes of breast cancer. Finally, there are triple negative tumors, which owe their name to the fact that they do not have any of the three receptors: neither for estrogen, nor for progesterone, nor for epidermal growth factor. Young patients tend to have this subtype, but it is not an absolute rule.

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The biopsy first of all

As it is easy to guess, knowing the type of cancer you are facing today is an essential step, because the treatment path depends on this information. “Never send a woman with breast cancer above one centimeter to the operating bed without first having a needle biopsy and waiting for the characterization of the subtype,” he says. Michelino De Laurentiis, director of the Department of Breast and Thoraco-Pulmonary Oncology at the National Cancer Institute IRCCS Pascale Foundation of Naples: “The diagnosis must always include histological characterization with needle biopsy or, in small tumors of one centimeter, cytological characterization with needle aspiration. In fact, in the case of triple negative and HER2-positive tumors greater than one centimeter, the best way forward is another: treat the tumor before surgery “.

What is neoadjuvant therapy

Doctors refer to this approach as “neoadjuvant” (to distinguish it from adjuvant therapy, which is given after surgery). There are three possibilities: the tumor disappears completely, which means that it will no longer be detectable during the operation; the tumor does not disappear, but is reduced; the tumor does not respond to drugs. “In this way we can see directly and in real time if the therapies administered work”, explains De Laurentiis: “If the tumor does not disappear but traces of it are still found during surgery, it means that there are resistant tumor cells. to that treatment. Knowing it allows us to change drugs in the post-surgical phase, and thus increase the chances of recovery “. In addition, immunotherapy drugs are on the way for triple negative tumors that can only be used before surgery. “So not adopting this procedure means denying the patients the opportunities for healing”, underlines the oncologist “.

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Immunotherapy before surgery for triple negative

At the latest San Antonio Breast Cancer Symposium, which was held last December, new data was presented on pembrolizumab, an immunotherapy already approved in many other cancers. The study involved nearly 1,200 patients with early stage (II and III) triple negative cancers, who were divided into two groups. All received neoadjuvant therapy before surgery for 12 weeks: one group received pembrolizumab and chemotherapy, the other a placebo and chemotherapy. After 36 months, the percentage of women who did not relapse was 84.5% and 76.8%, respectively.

“The combination of pembrolizumab plus chemotherapy led to the disappearance of the tumor before surgery in 65% of cases, a truly remarkable result”, comments De Laurentiis: “The study is very large and clearly indicates that the combination for neoadjuvant treatment the long-term prognosis clearly improves. After 36 months there has been a 40% reduction in the risk of relapse. These are not preliminary data, on the contrary: we can consider them almost definitive. And they allow us to hope to be able to increase the rate in the future of healing of this type of tumor “. This possibility is approved in the US, but not yet in Europe and Italy.

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Her2-positive targeted drugs

Also for patients with Her2-positive tumors, new drugs for neoadjuvant therapy are on the horizon, including conjugated monoclonal antibodies, capable of transporting chemotherapy molecules directly to the tumor. “Currently, neoadjuvant therapy is always indicated for patients with Her2-positive carcinoma in the initial stage and greater than 1-2 centimeters”, explains the expert: “In Italy, the combination of the targeted drug trastuzumab with chemotherapy is currently reimbursed. However, clinical studies have shown that adding another targeted drug, pertuzumab, to this combination brings an additional benefit. “

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The triplet pertuzumab-trastuzumab-chemotherapy is approved as neoadjuvant therapy in the European Union, but not in Italy. “Ours is one of the very few countries in Europe where it is not possible to use pertuzumab before surgery – comments De Laurentiis – and it is not clear why, since it is approved for post-surgical treatment. I am strongly convinced. which brings an advantage, so much so that it has requested and obtained from the Campania region to create an ad hoc fund “.

Always rely on a breast center

The research is progressing quickly and the landscape is destined to change yet again. However, the message remains: “Running to the surgeon can be a mistake”, concludes De Laurentiis: “Also for this reason it is important to always rely on a Breast Unit, that is to multidisciplinary breast care centers, where different specialists work in teams, discuss and are mainly or exclusively dedicated to the diagnosis and treatment of breast cancer “.

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