La svolta  da uno studio americano sui tumori al seno
Per curare il cancro stop  a rimozione dei linfonodi metastatici dell'ascella

DI ELISABETTA IOVINE  fonte: italia oggi

 
Dagli Stati Uniti arriva una novità in
tema di lotta ai tumori della mammella 

Uno studio
finanziato dall Istituto nazionale del
cancro evidenzia che molte donne alle
quali sia stata fatta una diagnosi precoce di
tumore al seno non
hanno più bisogno di
sottoporsi  nella   cura di routine della rimozione dei linfonodi ammalati
dell' ascella
Si tratta di una
rivoluzione nel  trattamento   di queste  forme
tumorali visto che
le cure tradizionali vanno avanti da
un secolo certi chein questo modo sia
possibile allungare la vita evitando
che la malattia si
sviluppi o riprenda il suo corso

I ricercatori
americani ora hanno annunciato che in circa
il 20 delle pazienti l eliminazione dei nodi
non dà alcun vantaggio non cambia il piano di
cura non migliora la sopravvivenza e non rende
meno probabile il ritorno del tumore

Oltretutto può provocare complicazioni come infezioni
e ostruzione linfatica un gonfiore cronico del
braccio che può diventare invalidante
La pratica di asportazione dei linfonodi è ba
sata sul fatto che una volta che il cancro abbia
raggiunto i nodi diventa più probabile l esten
sione della malattia agli organi vitali e a quel
punto non sia più possibile limitarsi a cure
ambulatoriali come la radioterapia e la chemio
terapia Non è la prima volta che si assiste a
un cambio di direzione nella cura del cancro al
seno Gli interventi chirurgici di mastectomia
l asportazione totale del seno cominciarono a
diminuire negli anni 1980
Questi mutamenti riflettono una mentalità
nuova nell approccio alla malattia
Negli scorsi decenni si era convinti
della bontà dellarimozione delle
masse tumorali era
necessario toglierle
di mezzo drasticamente prima che
attaccassero organi e ossa

Ma glistudi hanno dimostrato che il tumore
al seno è in gradodi diffondersi presto anche quando è piccolo
lasciando tracce microscopiche della malattia dopo
l intervento chirurgico L' approccio moderno è
quello di continuare a operare quando i tumori
sono evidenti lasciando a radio e chemioterapia
il compito di eliminate tracce microscopiche in
altre zone del corpo dove potrebbero svilupparsi
metastasi
Per quanto riguarda il cancro al seno alle
donne che rientrano nella nuova casistica  e' bastato  rimuovere al massimo uno o pochi linfonodi
continuando poi le altre forme di trattamento
Lo studio ha coinvolto poco meno di 900 pazienti in 115 centri medici degli Stati Uniti
 

Lymph Node Study Shakes Pillar of Breast Cancer Care

fonte : new york times

By DENISE GRADY

A new study finds that many women with early breast cancer do not need a painful procedure that has long been routine: removal of cancerous lymph nodes from the armpit.

The discovery turns standard medical practice on its head. Surgeons have been removing lymph nodes from under the arms of breast cancer patients for 100 years, believing it would prolong women’s lives by keeping the cancer from spreading or coming back.

Now, researchers report that for women who meet certain criteria — about 20 percent of patients, or 40,000 women a year in the United States — taking out cancerous nodes has no advantage. It does not change the treatment plan, improve survival or make the cancer less likely to recur. And it can cause complications like infection and lymphedema, a chronic swelling in the arm that ranges from mild to disabling.

Removing the cancerous lymph nodes proved unnecessary because the women in the study had chemotherapy and radiation, which probably wiped out any disease in the nodes, the researchers said. Those treatments are now standard for women with breast cancer in the lymph nodes, based on the realization that once the disease reaches the nodes, it has the potential to spread to vital organs and cannot be eliminated by surgery alone.

Experts say that the new findings, combined with similar ones from earlier studies, should change medical practice for many patients. Some centers have already acted on the new information. Memorial Sloan-Kettering Cancer Center in Manhattan changed its practice in September, because doctors knew the study results before they were published. But more widespread change may take time, experts say, because the belief in removing nodes is so deeply ingrained.

“This is such a radical change in thought that it’s been hard for many people to get their heads around it,” said Dr. Monica Morrow, chief of the breast service at Sloan-Kettering and an author of the study, which is being published Wednesday in The Journal of the American Medical Association. The National Cancer Institute paid for the study.

Doctors and patients alike find it easy to accept more cancer treatment on the basis of a study, Dr. Morrow said, but get scared when the data favor less treatment.

The new findings are part of a trend to move away from radical surgery for breast cancer. Rates of mastectomy, removal of the whole breast, began declining in the 1980s after studies found that for many patients, survival rates after lumpectomy and radiation were just as good as those after mastectomy.

The trend reflects an evolving understanding of breast cancer. In decades past, there was a belief that surgery could “get it all” — eradicate the cancer before it could spread to organs and bones. But research has found that breast cancer can begin to spread early, even when tumors are small, leaving microscopic traces of the disease after surgery.

The modern approach is to cut out obvious tumors — because lumps big enough to detect may be too dense for drugs and radiation to destroy — and to use radiation and chemotherapy to wipe out microscopic disease in other places.

But doctors have continued to think that even microscopic disease in the lymph nodes should be cut out to improve the odds of survival. And until recently, they counted cancerous lymph nodes to gauge the severity of the disease and choose chemotherapy. But now the number is not so often used to determine drug treatment, doctors say. What matters more is whether the disease has reached any nodes at all. If any are positive, the disease could become deadly. Chemotherapy is recommended, and the drugs are the same, no matter how many nodes are involved.

The new results do not apply to all patients, only to women whose disease and treatment meet the criteria in the study.

The tumors were early, at clinical stage T1 or T2, meaning less than two inches across. Biopsies of one or two armpit nodes had found cancer, but the nodes were not enlarged enough to be felt during an exam, and the cancer had not spread anywhere else. The women had lumpectomies, and most also had radiation to the entire breast, and chemotherapy or hormone-blocking drugs, or both.

The study, at 115 medical centers, included 891 patients. Their median age was in the mid-50s, and they were followed for a median of 6.3 years.

After the initial node biopsy, the women were assigned at random to have 10 or more additional nodes removed, or to leave the nodes alone. In 27 percent of the women who had additional nodes removed, those nodes were cancerous. But over time, the two groups had no difference in survival: more than 90 percent survived at least five years. Recurrence rates in the armpit were also similar, less than 1 percent. If breast cancer is going to recur under the arm, it tends to do so early, so the follow-up period was long enough, the researchers said.

One potential weakness in the study is that there was not complete follow-up information on 166 women, about equal numbers from each group. The researchers said that did not affect the results. A statistician who was not part of the study said the missing information should have been discussed further, but probably did not have an important impact.

It is not known whether the findings also apply to women who do not have radiation and chemotherapy, or to those who have only part of the breast irradiated. Nor is it known whether the findings could be applied to other types of cancer.

The results mean that women like those in the study will still have to have at least one lymph node removed, to look for cancer and decide whether they will need more treatment. But taking out just one or a few nodes should be enough.

Dr. Armando E. Giuliano, the lead author of the study and the chief of surgical oncology at the John Wayne Cancer Institute at St. John’s Health Center in Santa Monica, Calif., said: “It shouldn’t come as a big surprise, but it will. It’s hard for us as surgeons and medical oncologists and radiation oncologists to accept that you don’t have to remove the nodes in the armpit.”

Dr. Grant W. Carlson, a professor of surgery at the Winship Cancer Institute at Emory University, and the author of an editorial accompanying the study, said that by routinely taking out many nodes, “I have a feeling we’ve been doing a lot of harm.”

Indeed, women in the study who had the nodes taken out were far more likely (70 percent versus 25 percent) to have complications like infections, abnormal sensations and fluid collecting in the armpit. They were also more likely to have lymphedema.

But Dr. Carlson said that some of his colleagues, even after hearing the new study results, still thought the nodes should be removed.

“The dogma is strong,” he said. “It’s a little frustrating.”

Eventually, he said, genetic testing of breast tumors might be enough to determine the need for treatment, and eliminate the need for many node biopsies.

Two other breast surgeons not involved with the study said they would take it seriously.

Dr. Elisa R. Port, the chief of breast surgery at Mount Sinai Medical Center in Manhattan, said: “It’s a big deal in the world of breast cancer. It’s definitely practice-changing.”

Dr. Alison Estabrook, the chief of the comprehensive breast center at St. Luke’s-Roosevelt hospital in New York said surgeons had long been awaiting the results.

“In the past, surgeons thought our role was to get out all the cancer,” Dr. Estabrook said. “Now he’s saying we don’t really have to do that.”

But both Dr. Estabrook and Dr. Port said they would still have to make judgment calls during surgery and remove lymph nodes that looked or felt suspicious.

The new research grew out of efforts in the 1990s to minimize lymph node surgery in the armpit, called axillary dissection. Surgeons developed a technique called sentinel node biopsy, in which they injected a dye into the breast and then removed just one or a few nodes that the dye reached first, on the theory that if the tumor was spreading, cancer cells would show up in those nodes. If there was no cancer, no more nodes were taken. But if there were cancer cells, the surgeon would cut out more nodes.

Although the technique spared many women, many others with positive nodes still had extensive cutting in the armpit, and suffered from side effects.

“Women really dread the axillary dissection,” Dr. Giuliano said. “They fear lymphedema. There’s numbness, shoulder pain, and some have limitation of motion. There are a fair number of serious complications. Women know it.”

After armpit surgery, 20 percent to 30 percent of women develop lymphedema, Dr. Port said, and radiation may increase the rate to 40 percent to 50 percent. Physical therapy can help, but there is no cure.

The complications — and the fact that there was no proof that removing the nodes prolonged survival — inspired Dr. Giuliano to compare women with and without axillary dissection. Some doctors objected. They were so sure cancerous nodes had to come out that they said the study was unethical and would endanger women.

“Some prominent institutions wouldn’t even take part in it,” Dr. Giuliano said, though he declined to name them. “They’re very supportive now. We don’t want to hurt their feelings. They’ve seen the light.”

Il New York Times due giorni fa ha dato ampio spazio in prima pagina all’annuncio di un nuovo progresso nella cura del tumore del seno: l’intervento chirurgico di rimozione dei linfonodi dell’ascella, anche se colpiti dalla malattia, non deve più essere lo standard per tutte le pazienti. A molti forse è sfuggita l’importanza di questo messaggio, che ha invece un significato speciale per le donne e per la ricerca scientifica italiana. Per le donne perché è dimostrato che sono le migliori custodi della propria salute: con la loro consapevolezza e determinazione sono in grado di far crollare la rigidità dei dogmi e scuotere la mentalità conservatrice di alcuni medici.

Se sanno che esiste una cura migliore per loro, prima o poi la otterranno. Per la ricerca italiana, perché esattamente 30 anni fa sullo stesso giornale e nella stessa posizione, appariva la notizia della strada aperta da noi chirurghi italiani per le donne, di cui l’annuncio dei giorni scorsi rappresenta una nuova tappa. Nel luglio del 1981, infatti, proprio il New York Times (insieme ad altri quotidiani americani come Los Angeles Times ed Herald Tribune) riportava una rivoluzione fondamentale per le donne colpite da tumore del seno.

Il dogma della mastectomia (asportazione totale della mammella), che si poneva l’obiettivo di salvare la vita della paziente, era stato superato dalla nuova tecnica della quadrantectomia (asportazione di una parte, un quadrante, della mammella) che non solo salvava la vita, ma ne preservava anche qualità. Il risultato, spiegava l’articolo, era dovuto agli «italian doctors» che avevano appena pubblicato sul New England Journal of Medicine gli esiti di uno studio clinico durato sette anni e realizzato a Milano. Sono felice di avere fortemente voluto quello studio e di aver firmato quella pubblicazione scientifica, perché cambiando la direzione del trattamento del tumore del seno, ha cambiato la vita delle donne.

Poi abbiamo capito all’Istituto Europeo di Oncologia che potevano spingerci più in là nella protezione dell’integrità del corpo della donna e, oltre alla mammella ci siamo chiesti se potevano salvare l’ascella, evitando ove possibile l’intervento di rimozione dei suoi linfonodi. Così abbiamo messo a punto la tecnica del linfonodo sentinella, vale dire quel linfonodo che è in grado di darci indicazioni sullo stato di tutti gli altri. Se è sano, l’ascella è sana, se è malato, l’ascella è malata. Abbiamo iniziato a effettuare gli interventi all’ascella solo in caso di linfonodo sentinella malato, risparmiando così operazioni non necessarie alle nostre pazienti, e evitando di privarle di una parte preziosa della loro difesa immunitaria. La notizia americana ci incoraggia e rafforza i nostri capisaldi, andando ancora oltre nella strategia della conservazione: la rimozione dei linfonodi dell’ascella, anche se malati, non deve necessariamente essere effettuato, per certi specifici tipi di tumori (pari al 20% circa di tutti i casi) perché non porta vantaggi nella cura.

Si profila sempre più chiaramente quindi il tramonto del concetto stesso di dogma in medicina. La cura si fa personalizzata e già siamo molto vicini a poter offrire ad ogni donna con tumore del seno un percorso di cura individuale. E per far crollare i dogmi, l’abbiamo detto, contiamo molto sulla forza delle donne.

Umberto Veronesi su La Stampa

Axillary Dissection vs No Axillary Dissection in Women With Invasive Breast Cancer and Sentinel Node Metastasis

 JAMA. 2011;305(6):569-575. doi: 10.1001/jama.2011.90

A Randomized Clinical Trial

Abstract

Context Sentinel lymph node dissection (SLND) accurately identifies nodal metastasis of early breast cancer, but it is not clear whether further nodal dissection affects survival.

Objective To determine the effects of complete axillary lymph node dissection (ALND) on survival of patients with sentinel lymph node (SLN) metastasis of breast cancer.

Design, Setting, and Patients The American College of Surgeons Oncology Group Z0011 trial, a phase 3 noninferiority trial conducted at 115 sites and enrolling patients from May 1999 to December 2004. Patients were women with clinical T1-T2 invasive breast cancer, no palpable adenopathy, and 1 to 2 SLNs containing metastases identified by frozen section, touch preparation, or hematoxylin-eosin staining on permanent section. Targeted enrollment was 1900 women with final analysis after 500 deaths, but the trial closed early because mortality rate was lower than expected.

Interventions All patients underwent lumpectomy and tangential whole-breast irradiation. Those with SLN metastases identified by SLND were randomized to undergo ALND or no further axillary treatment. Those randomized to ALND underwent dissection of 10 or more nodes. Systemic therapy was at the discretion of the treating physician.

Main Outcome Measures Overall survival was the primary end point, with a noninferiority margin of a 1-sided hazard ratio of less than 1.3 indicating that SLND alone is noninferior to ALND. Disease-free survival was a secondary end point.

Results Clinical and tumor characteristics were similar between 445 patients randomized to ALND and 446 randomized to SLND alone. However, the median number of nodes removed was 17 with ALND and 2 with SLND alone. At a median follow-up of 6.3 years (last follow-up, March 4, 2010), 5-year overall survival was 91.8% (95% confidence interval [CI], 89.1%-94.5%) with ALND and 92.5% (95% CI, 90.0%-95.1%) with SLND alone; 5-year disease-free survival was 82.2% (95% CI, 78.3%-86.3%) with ALND and 83.9% (95% CI, 80.2%-87.9%) with SLND alone. The hazard ratio for treatment-related overall survival was 0.79 (90% CI, 0.56-1.11) without adjustment and 0.87 (90% CI, 0.62-1.23) after adjusting for age and adjuvant therapy.

Conclusion Among patients with limited SLN metastatic breast cancer treated with breast conservation and systemic therapy, the use of SLND alone compared with ALND did not result in inferior survival.

N Engl J Med. 2011 Feb 3;364(5):412-21. Epub 2011 Jan 19.

Effect of occult metastases on survival in node-negative breast cancer.

Weaver DL, Ashikaga T, Krag DN, Skelly JM, Anderson SJ, Harlow SP, Julian TB, Mamounas EP, Wolmark N.

University of Vermont College of Medicine and Vermont Cancer Center, Department of Pathology, Burlington, VT 05405-0068, USA. donald.weaver@vtmednet.org