临床显著的乳腺病变管理

乳房“肿块”和乳房疼痛

影像学对于临床显著的病变的作用，我认为目前还没有形成明确的共识。根据我的经验，大多数女性是因为疼痛才第一次仔细“检查”乳腺并发现有肿块或增生的。由于疼痛，正常的“肿块”乳腺组织也会被患者认为是不正常的。但事实上乳腺癌很少引起疼痛，与癌症相关的疼痛属于偶发。

有时，有的病人无法区分乳房疼痛和胸壁疼痛（例如：肋软骨炎）。如果乳房在被往胸壁推压时有疼痛，但在乳房被侧向推压（或从上到下）时没有疼痛，那么很可能是胸壁疼痛而不是乳房疼痛。

有时我看到一些癌症会伴随“牵拉”的感觉，好像有什么东西从乳房内被拉扯出来。不过，可触感的囊肿或脓肿也可能会引起类似疼痛。

影像学评价

为避免混淆，我总是会在阅片报告中首先写明：“在患者所指的临床症状的位置”或“…如病史所示”，然后再提供我的评估。

当用影像评估一个临床关注的位置时，我们的首要任务是：确定是否存在一个真实的病变，还是那只是感觉到有不均匀的、块状乳腺组织。 当然，当乳腺X射线摄影所显示临床关注区域全部是脂肪时，存在恶性肿瘤的可能性非常小（我在40多年中只见过一个案例）。如果乳腺X射线摄影显示该位置全是脂肪，我就不会建议继续做超声检查。

我从未对于临床显著病变使用BIRADS 3分类。目前还没有可靠的文献阐述如何管理临床症状显著、但被影像学检查归类为BIRADS 3的案例。我个人认为临床评估是有其作用的，因此当我评估一个临床明显的肿块时，即使它看上去不太令人担心，但在提供影像分析评估时（我知道乳腺X射线摄影的阴性并不能完全排除存在癌症可能性），我仍然会说明：“任何进一步措施的决定，都应基于目前的临床评估”。

最终评估

多年前我们发现，如果乳房检查部位不全是脂肪，即使乳腺X射线摄影和乳腺超声检查结果均为阴性，那么患癌的可能性（尽管极低）也不是零 ¹。我认为BIRADS 3也可能适用于这样的评估。有少数的乳腺恶性肿瘤看起来像纤维腺瘤。我个人认为核芯针活检是非常安全和准确的。我更倾向于不依赖影像学检查结果，并建议使用影像学引导的穿刺活检来确定实性肿块的病理结果。如果你有经验丰富的外科医生，他们可以在门诊使用局部麻醉或清醒镇静，进行非常安全的并考量美观效果的乳房手术，我会敦促切除任何不确定、可触及的实性肿块。这对于年轻女性来说尤其如此，可触及肿块几乎可以肯定是纤维腺瘤，但随着年龄的增长，她们可能会需要接受反复的影像学检查和空芯针穿刺活检，而新的医生在临床检查中无法确定病变是否稳定，而且不能进行影像学变化对比。

影像学的作用

我认为重要的是，要认识到并强调：乳腺X射线摄影几乎完全是一种筛查检查手段²。它的主要价值，也许是唯一的（也最基本的）价值，是在乳腺癌临床上变得明显之前，检测出乳腺癌，此时治愈的可能性更大。了解了这一点，就容易理解我们很久前就确定的一个事实：当女性乳腺出现临床明显的异常时，乳腺X射线摄影在评估临床明显的病变方面价值并不大；但是，它的重要作用是，筛查该侧乳房的其余部分和对侧乳房是否存在未被发现的恶性病灶³。乳腺X射线摄影所显示出的“典型癌症”，可以避免临床医生忽略该病变。但事实上，除了少数例外，如钙化、退化型纤维腺瘤；钙乳囊肿；或边缘清晰的含有脂肪的病变（如脂肪瘤和错构瘤），乳腺X射线摄影很少能够准确判断临床上明显的良性病变。

超声具有一个相当独特的作用：它能够容易地确定一个病变（临床上明显的或隐匿的）是一个单纯的囊肿，因此不用担心有什么问题。这可能就足以避免进一步的干预措施。但常被忽视的一件事是：在临床指导下对可触及的病变进行抽吸，通常比超声检查的费用要低。通过引流囊肿，不仅可以确定良性诊断，而且可以消除患者对 “肿块”的担忧。尽管临床指导下的囊肿抽吸术是安全和容易的（而且成本较低），但我认为，目前美国大多数情况还是在靠超声检查结果。

区分良性恶性

虽然已有一些超声的征象标准，在超声上观察到这些增加了良性可能性。但实际上每一个“良性征象”，也会在一些恶性病变案例中出现。我个人并不凭借超声来区分实性肿块的良恶性，但的确有很多人在这样做。虽然已经制定了一些征象标准，这些征象在超声上的出现就增加了其被定性为良性的可能性，但实际上每一个“良性”征象也都可以出现在恶性病变中。我个人并不依赖超声来区分实性肿块的良恶性，但有很多人会这样做。

如果病人有三个或更多相同类似的看似良性病变，我会遵循Sickles的 “多发性规则”。如果有三个或更多同种病变（除非具有恶性特征的肿块，如边缘不规则或带毛刺），它们几乎都是良性的，不需要进一步评估。

年轻女性

筛查的随机对照试验（RCT）已经证明，早期发现可以挽救年龄在40-74岁妇女的生命（参加试验的女性年龄）。没有任何数据显示，任何筛查参数的界限/决定因素（包括挽救的生命）会在50岁时突然改变。从40岁开始筛查是临床科学证实确认（可以降低乳腺癌死亡率）的年龄。而50岁开始筛查，是完全随意的起始值，没有科学依据。

最近一篇论文，声称对40岁以下有明显临床症状的女性进行了评估，结论是只需要做超声检查即可⁴。他们的结论是：首先使用超声检查（而且通常不做乳腺X射线摄影），我认为是错误的，并且这个结论没有数据支持⁵。事实上，他们的乳腺X射线摄影发现隐匿性癌症的比率，与40岁出头时接受常规筛查的女性相似，而且很可能挽救生命。与他们的结论相反：对于存在临床症状的女性，应在30岁及以上（35岁及以上，更应如此）进行乳腺X射线摄影检查（并在有问题位置放置“BB”标记）。理想情况是，标记物在CC位影像中的位置与病灶重叠；并在MLO位时情况也相同。在两个投影中，“BB”标记应该置于病变的上方。

有人对40岁以下女性筛查提出了疑问。由于没有针对40岁以下女性人群的RCT研究，所以没有“证据”证明早期发现这些女性的癌症会挽救生命。可能的情况是：如果筛查年轻女性人群可行，那么也可挽救这个人群的生命。事实上，人们在纽约纪念斯隆凯特琳癌症中心医院多年前对于首次筛查年龄为35岁的乳腺X射线摄影的研究中发现30岁女性癌症检出率为1.4/1000⁶，与40岁出头的女性发病率相同。

Yankaskas等人也得到类似的结果⁷。不合常理的是，有些人认为三十多岁的女性如果出现临床症状，是不需要做乳腺X射线摄影的（尽管他们发现乳腺X射线摄影发现的隐匿性癌症的比率高达2/1000）。这些人忽视了这样一个事实：对于年轻女性来说，对已经发现的病灶成像几乎没有什么附加价值；但通过乳腺X射线摄影，在乳房内其它区域发现之前未检测到的恶性病变会挽救生命⁸。

辐射风险

人们对三十多岁的妇女接受乳腺检查的辐射风险表示担忧。对于十几岁和二十几岁的女性来说，辐射风险是一个令人担忧。但到30岁时辐射风险会迅速下降，到40岁时辐射风险就低到无法计量了。即使用外推法计算，40岁人群的辐射风险也低到，乃至于微小的临床收益也超过了该风险。当然，如果我们提倡对30-39岁的女性进行常规乳腺X射线摄影，辐射剂量可能是一个问题。但对这个年龄组中相对较少的、有临床问题的女性进行乳腺X射线摄影，则不太可能有任何重大风险，而且这会挽救生命。

结论

鉴于早期发现的重要性，并考虑到安全和准确地进行活检和/或手术切除病变的能力，我认为无论临床显著的实性病变外观如何，都最好要进行活检或切除（尤其是40岁以下的女性），除非病变中明显钙化或是含有脂肪的良性病变。

中英翻译

THE MANAGEMENT OF CLINICALLY EVIDENT BREAST LESIONS

“LUMPS” AND BREAST PAIN

I don’t think there is a clear consensus on the role of imaging for clinically evident findings. In my experience most women who present with a lump or thickening initially “found” the area because it was sore and they carefully “examined” the area for the first time. Because of the pain, the “lumpy” normal, but “sore”, breast tissue was perceived as being abnormal to the patient. Breast cancer rarely causes pain. If there is pain associated with a cancer it may be coincidental.  

At times a patient is unable to differentiate pain in the breast from chest wall pain (eg: costochondritis). If there is pain when the breast is pushed back against the chest wall, but not when the breast is compressed side to side (or top to bottom), then it is likely chest wall pain and not breast pain.

On occasion I have seen a few cancers that were associated with a ‘‘drawing’’ sensation, as if something was pulling from within the breast. Conversely, a palpable cyst or an abscess may cause pain.  

IMAGING EVALUATION

To avoid confusion, I always begin by stating in my report, “In the area of clinical concern as indicated by the patient” or “….as indicated by the history” and then provide my assessment.  

When evaluating an area of clinical concern with imaging our first role is to try to determine if there is actually a definable lesion or are they simply feeling heterogenous, “lumpy”, breast tissue. Certainly, when the mammogram shows all fat in the area of clinical concern, a malignancy is very unlikely (I have seen one case in 40+ years). If the area is all fat on the mammogram, I do not proceed to ultrasound. 

I have never used BIRADS 3 for a clinically evident lesion. I don’t think there is much useful literature on the management of clinically evident lesions that undergo imaging and are categorized as BIRADS 3. Since I still feel that there is a role for clinical evaluation, when I evaluate a clinically evident mass and I provide my imaging analysis and explain that I am not concerned by the imaging findings, but knowing that a negative mammogram does not exclude cancer, I still qualify my report by stating:

“Any decision for further intervention, at this time, should be based on the clinical assessment”.

ULTIMATE ASSESSMENT

Years ago we found that even if the mammogrpahy and ultrasound together are negative, the likelihood of a cancer, although still very low, is not zero ¹, assuming that the area is not all fat on the mammogram. I suspect that this also goes for what seem to be BIRADS 3 lesions as well. There are a small number of malignancies in the breast that look like fibroadenomas. I personally feel that core biopsy is very safe and accurate, and I prefer to not rely on imaging findings, but would recommend an imaging guided needle biopsy to determine the pathology of a solid mass. If you have highly skilled surgeons who can perform breast surgery very safely in an outpatient setting using local anesthesia or conscious sedation and with good cosmetic results, I would urge the removal of any, indeterminate, palpable solid masses.  This is especially true in younger women with a palpable mass which is almost certainly a fibroadenoma, but who may end up with repeated imaging and needle biopsies as they age and see new physicians who cannot be certain that the lesion is stable on their clinical examination and imaging comparisons may not be available. 

THE ROLE OF IMAGING

I think it is important to recognize and emphasize that mammography is, almost exclusively, a screening test ². Its main and perhaps only (but fundamental) value is the detection of breast cancers before they become clinically evident at a time when cure is more likely. Once that is understood, we long ago established the fact that when a woman presents with a clinically evident abnormality, mammography has little value in assessing the clinically evident lesion, but it has the important role of screening the rest of that breast and the contralateral breast for unsuspected malignancies ³. The mammographic demonstration of a “classic” cancer can prevent the unlikely chance that the clinician might decide to ignore the lesion, but, in fact, with a few exceptions such as a calcified, involuting fibroadenoma; cysts defined by milk of calcium; or well marginated lesions that contain fat (eg. lipomas and hamartomas), mammography is rarely able to accurately determine that something that is clinically evident is benign. 

Ultrasound has a fairly unique role in its ability to easily demonstrate that a lesion (clinically evident or occult) is a simple cyst and therefore of no concern. This may suffice to avoid further intervention. What has been ignored is the fact that a clinically guided aspiration of a palpable lesion is usually less expensive than ultrasound, and by draining a cyst not only is a benign diagnosis established, but it removes the “lump” as a concern to the patient. Despite the safety and ease (and lower cost) of a, clinically guided, cyst aspiration I suspect that most in the U.S., nevertheless, now rely on the ultrasound results.  

TELLING BENIGN FROM MALIGNANT

Although criteria have been developed whose presence on ultrasound increase the likelihood that a finding is benign, virtually every “benign” criterion can be found, on occasion, in malignant lesions. I personally do not rely on ultrasound to differentiate benign from malignant solid masses, but there are many who do.

If the patient has three or more similarly benign appearing lesions, I follow Sickles’ “rule of multiplicity”. If there are three or more of the same lesion (with the exception of masses with malignant characteristics such as irregular or spiculated margins), they are almost always benign and do not require further evaluation.   

YOUNG WOMEN

The randomized controlled trials (RCT) of screening have proven that early detection saves lives for women ages 40-74 (the ages of the women who participated in the trials). There are no ungrouped/unaveraged data that show that any of the parameters of screening, including lives saved, change abruptly at the age of 50. Age 40 is the scientifically derived age to initiate screening. The age of 50 is a completely arbitrary threshold with no scientific support. 

A recent paper claiming to evaluate women under the age of 40 with a clinically evident problem concluded that ultrasound was all that was needed ⁴. I think their conclusion to use ultrasound first (and often without mammography) was misguided and not supported by their data ⁵. In fact, their mammography identified occult cancer at a similar rate to that for women being routinely screened in their early 40’s and was likely lifesaving.  Contrary to their conclusions, mammography should be done in women ages 30 and over (certainly age 35 and over) for those who present with an area of clinical concern (with a “BB” marker placed on the area of concern). Ideally, the marker should be placed so that it overlies the lesion on the CC projection and moved so that the same is true on the MLO projection. The “BB” should be “on top of the lesion” in both projections.

Questions have been raised about screening women under the age of 40.  Since there are no RCT’s of women under the age of 40 there is no “proof” that finding cancers in these women earlier will save lives, but it is likely that, were it feasible, screening younger women would also save lives. In fact, in a study from Memorial in New York years ago when we used to obtain “baseline” mammograms at the age of 35, the investigators found, not surprisingly, that the cancer detection rate for women in their late 30’s was 1.4/1000 ⁶ which was the same rate as for women in their early 40’s. Yankaskas et al had similar results ⁷. Incongruously, some have argued that mammography is not needed for women in their thirties who present with a clinical area of concern, despite the fact that they find occult cancer detection rates of up to 2/1000 found by mammography. These authors ignored the fact that, with regard to young women, imaging of the lesion itself has little added value and, once again, the discovery of an unsuspected malignancy by mammography elsewhere in the breast may be lifesaving ⁸. 

RADIATION RISK

Concerns have been raised about the radiation risk from mammogrpahy among women in their thirties. Radiation risk is a concern for women in their teens and early twenties, but it drops off rapidly by age 30 and is unmeasurable by the age of 40.  Even the extrapolated risk by age 40 is so small that it is outweighed by even the smallest benefit. Certainly, if we advocated for routine mammography screening for women ages 30-39, the radiation might be a concern, but performing mammograms on the, relatively, small number of women in this age group who present with clinical concerns is unlikely to carry any major risk and may well be lifesaving. 

CONCLUSION

Given the importance of early detection and given the ability to biopsy and/or surgically remove lesions safely and accurately, I think it is best to at least biopsy clinically evident solid lesions, or to remove solid breast lesions regardless of their appearance (particularly in women under the age of 40) unless the lesion is clearly calcified or a circumscribed fat containing benign lesion.  

REFERENCES

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2.Kopans DB. Breast imaging and the standard of care for the symptomatic patient. Radiology. 1993 Jun; 187(3):608-11.

3.Kopans DB, Meyer JE, Cohen AM, Wood WC. Palpable breast masses. The importance of preoperative mammography. JAMA. 1981 Dec 18; 246(24):2819-22. 

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5.Doi.org/10.2214/AJR.18.20776   AJR:212, May 2019

6.Liberman L, Dershaw DD, Deutch BM, et al. Screening mammography: value in women 35–39 years old. AJR Am J Roentgenol 1993; 161:53–56.

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8.Doi.org/10.2214/AJR.18.20776   AJR:212, May 2019