基线因素对乳房切除术决策的影响更大

维也纳——在欧洲肿瘤内科学会(ESMO)年会上报告的对Neo ALLTO试验数据的最新分析表明，是否行保乳手术(BCS)取决于患者基线特征，而非治疗应答效果。

米兰欧洲肿瘤研究所的Carmen Criscitiello博士报告称，基线时肿瘤多中心病灶/多灶性、受体状态以及确诊时计划手术类型均影响决定实施BCS还是乳房切除术。他呼吁大家对新辅助治疗应答患者行BCS达成明确共识，并最终将新辅助治疗的进步转化为保乳率的提高。

保乳手术率低令人困惑

Criscitiello博士认为，新辅助治疗具有检测全身治疗的敏感性、降低肿瘤分期以便适合手术、消除微转移以及提高保乳率等多方面的潜在作用。因此，期望能够在Neo ALLTO [拉帕替尼和(或)曲妥珠单抗新辅助治疗方案优化试验]试验中看到BCS率有明显提高。

在这项HER2阳性早期乳腺癌患者新辅助治疗方案Ⅲ期试验中，半数患者在紫杉醇治疗基础上接受2种HER2抑制剂拉帕替尼(泰克博)和曲妥珠单抗(赫赛汀)治疗后达到了病理学完全应答(pCR)，但大部分患者(58.6%)仍然接受乳房切除术，而没有选择BCS。

在该项研究中接受其他治疗方案患者的BCS率也与之相似，令研究者感到困惑。接受拉帕替尼+曲妥珠单抗+紫杉醇、曲妥珠单抗+紫杉醇、拉帕替尼+紫杉醇方案治疗的患者达到pCR的比例分别为51.3%、29.5%和24.7%，而BCS率分别仅为41.4%、38.9%和 42.9%。

为了解更多女性没有选择BCS的原因，作者排除了未行乳房手术的26例患者后，对429例受试者资料进行了分析。通过查阅病历了解患者年龄、多中心病灶/多灶性、确诊时手术计划、术前体检、术前影像学检查、肿瘤特征以及地理区域等基线特征。

分析结果显示，如果患者已经计划行保乳治疗，则更多选择BCS而非切除术，她们的肿瘤分期较低(T2 vs. T4)，或者淋巴结状态分期较低(N0 vs. N+)。地理区域也较重要，发达国家患者比发展中国家患者更多选择保守治疗。相反，扩散程度严重、雌激素(ER)阴性以及残留病灶明显的患者更多选择切除术。

上述结果表明，新辅助治疗后手术治疗方式的选择依据主要是患者基线特征。研究者认为，发展中国家BCS率较低可能与缺少放疗条件有关。

pCR的确认可能是问题所在

伦敦皇家马斯登NHS基金会乳腺癌科主任、肿瘤内科顾问Ian Smith博士评论道：“令人失望的是，我们取得了较高的应答率，但仍有许多患者接受了切除术。”他认为，最关键的问题是确认是否已出现了pCR。

Smith博士指出，最根本的问题是外科医生在术前并不知道是否已经达到pCR，因此应考虑采取其他的指导方法。方法之一是应用Ki67等分子标志物。皇家马斯登医院的数据表明，新辅助化疗前后检测Ki67有助于确认可接受更保守的手术治疗的患者。“我们应该在新辅助治疗第1疗程结束后再次进行活检，利用分子标志物预测可能达到pCR的患者。如果患者达到pCR，她们可能只需小手术或无需手术。”

Neo ALTTO试验由葛兰素史克制药资助，但该公司没有参与该项分析研究。Criscitiello博士无利益冲突披露。

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By: SARA FREEMAN, Ob.Gyn. News Digital Network

VIENNA – The decision to undergo breast-conserving surgery depends on baseline characteristics rather than response to therapy, according to a new analysis of data from a phase III trial comparing neoadjuvant regimens for early HER2-positive breast cancer.

Baseline multicentricity or multifocality of the tumor, receptor status, and the type of surgery planned at diagnosis all were found to influence the decision to undergo breast-conserving surgery (BCS) or mastectomy, investigators reported Sept. 30 at the European Society for Medical Oncology Congress.

"These results call for a clear consensus on the role of breast-conserving surgery in patients responding to neoadjuvant therapy," Dr. Carmen Criscitiello told attendees.

"This will ultimately translate the progress in neoadjuvant therapies into improved breast conservation rates," suggested Dr. Criscitiello of the European Institute of Oncology in Milan.

Puzzled by Low BCS Rates

Neoadjuvant therapy has several possible roles, including testing sensitivity to systemic therapy, downstaging tumors to make them operable, eliminating micrometastases, and increasing breast conservation rates, Dr. Criscitiello explained. It was therefore expected that BCS rates would increase significantly in the Neo ALLTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) trial.

Half of all patients treated with a dual HER2 blockade of lapatinib (Tykerb) and trastuzumab (Herceptin) in addition to paclitaxel achieved a pathological complete response (pCR) in the Neo ALLTO trial. Yet the majority (58.6%) went on to have a mastectomy rather than BCS.

This puzzled investigators, who saw similar BCS rates in patients treated with other regimens in the study. All told, a pCR was achieved by 51.3% of patients treated with lapatinib, trastuzumab, and paclitaxel; 29.5% of those treated with trastuzumab and paclitaxel; and 24.7% given lapatinib and paclitaxel. Yet the respective rates of BCS were 41.4%, 38.9%, and 42.9%.

To investigate why more women did not opt for BCS, the authors examined data on 429 women who had participated in the trial, excluding 26 who did not undergo breast surgery. The records were examined for baseline characteristics including age, multicentricity/multifocality, planned surgery at diagnosis, physical examination before surgery, imaging before surgery, tumor characteristics, and geographic region.

Women were more likely to have BCS than mastectomy if breast-conserving treatment was already planned, they had a lower (T2 vs. T4) tumor grade, or their nodal (N0 vs. N+) status was lower. Geographic location was also important, with women treated in developed countries more likely to have more conservative treatment than those in developing regions.

Conversely, women were more likely to have a mastectomy than BCS if they had more diffuse disease, were estrogen receptor (ER)-negative, and had residual palpable disease.

"Our study suggests that the decision of surgical treatment post neoadjuvant therapy is mainly based on baseline characteristics," Dr. Criscitiello said. The lower rate of BCS in developing countries could be due to the lack of available radiotherapy, she observed.

Identifying pCR Could Be Hitch

"It is disappointing that we get high remission rates and yet a lot of women still have mastectomy," Dr. Ian Smith, commented after hearing these data.

Dr. Smith, a consultant medical oncologist and head of the Breast Unit at the Royal Marsden NHS Foundation Trust in London, noted that a key problem is identifying whether or not a pCR has occurred.