Welcome to First Incision, the podcast about preparing for the General Surgery Fellowship exam. I'm your host, Amanda Nikolic. Hello, and thanks for hanging out with me again today. I'm going to cover a few topics today, so let's go to our team timeout. The patient today is the breast module from the general surgical curriculum. We're not quite ready to move on yet. And our...
operation or topics we'll be covering today are special populations. So in particular, I mean pregnancy-associated breast cancer. I'll briefly discuss a couple of options for premenopausal women who have the potential to become pregnant who are diagnosed with breast cancer, as well as positive lymph node unknown primary breast cancer.
Starting with pregnancy-associated breast cancer. This is a... very upsetting diagnosis that involves diagnosis of breast cancer during pregnancy up to one year after delivery or during lactation. The pathophysiology of this condition is that it tends to be ERPR negative and the HER2 can either be positive or negative. It's typically high grade with evidence of lymphovascular invasion at diagnosis.
is a larger size and has nodal involvement at diagnosis compared to non-pregnancy associated breast cancer. The differential diagnosis of a breast mass in pregnancy is quite wide. And this is why these cancers often are diagnosed late as they are misdiagnosed or thought to be other causes of breast masses during pregnancy and lactation. The list of differentials includes a lactation adenoma.
fibroadenoma, cysts, lobular hyperplasia, a galactocele, an abscess, lipoma, hematoma, and obviously pregnancy-associated breast cancer. Workup of a woman who presents with a breast lump, whether they are pregnant or breastfeeding or not, involves a triple assessment. So this includes a history and examination. And the history should focus on risk factors for breast cancer, family history, and other things that we've talked about in our previous episodes.
Examination is the same for a pregnant or breastfeeding woman as it is for a woman presenting with a breast lump at any other time. Imaging can be a little bit more difficult because obviously we need to consider the developing fetus. So mammograms can be performed with shielding of the abdomen and this is thought to be a safe investigation. Ultrasound is also obviously safe for the fetus and can give good information about the mass as well as guide core biopsy.
Talking about core biopsy, this is the third step in a triple assessment and involves taking a core of the breast mass. It can be difficult to interpret a core biopsy in a lactating woman as there's increased proliferation and can be atypia in the cells of the breast just because of the lactation itself. important to include clinical information and your suspicions based on the radiological appearance of the mass when you send that biopsy off for the pathologist.
Some concern may be raised about the development of a milk fistula, which I've mentioned in the galactoseal episode. However, it's obvious that obtaining the diagnosis is much more important and outraised the... small risk of development of a milk fistula with a core biopsy in these cases.
If there is any evidence of clinically or radiologically suspicious nodes in the axilla, then they should also be biopsied with either an FNA or a core as you would in a non-pregnant or non-breastfeeding patient. If there is evidence of auxiliary node involvement or suspicion for metastatic disease, it is difficult to stage and do a metastatic workup with imaging in these patients because of the risk of radiation to the fetus.
So obviously a chest x-ray can be performed with abdominal shielding and is thought to be relatively safe. However, a CT chest, abdo pelvis is a very high dose radiation exposure to a developing fetus and is not really recommended in these cases. You can perform an MRI of the liver or of the whole body if required.
In some of the reading that I was doing is some concern that the gadolinium can cross the placenta and adversely affect the fetus in animals. But most of the guidelines that I read is that it's probably safe in pregnant women and can be used. a case discussion I had the other day in a tute, they did talk about that as being an option instead of a CT scan. PET scans haven't really been studied in pregnancy-associated breast cancer, so there's not really enough evidence for this.
Bone scans with lower doses of the radioisotope have been used but generally are not recommended. So it can be really difficult to do an in-depth metastatic workup for these patients. Moving on to treatment of pregnancy-associated breast cancer.
As I've said the whole way through, these patients should be discussed at an MDT and there are obvious difficulties both in the workup and management of patients who are pregnant or breastfeeding when it comes to treating breast cancer. In general, The treatment options are all the same as with non-pregnancy associated breast cancers.
There are some considerations though which I'll go into about when and what treatments can be used at different stages of pregnancy. So in general, surgery is an option for women with pregnancy-associated breast cancer. The best time to operate on these patients is in the second trimester, but obviously we don't have control over when they are diagnosed. The reason is that there is a small increase of risk miscarriage if you are given an anesthetic in the first trimester.
is small, so it doesn't completely preclude patients from having surgery in the first trimester. In patients who have a pregnancy associated breast cancer, the options include breast conserving surgery. or mastectomy the same way and with the same considerations of a patient who does not have pregnancy associated breast cancer. The key thing to know though is that you cannot give radiotherapy during pregnancy. The risk to the fetus is really high and that includes the...
high risk of development of a malignancy in childhood. So radiotherapy not being an option during pregnancy would guide whether or not you can offer breast conserving surgery because as I've discussed before, if a patient's going to have breast conservation surgery, then they need to have radiotherapy postoperatively. So for patients in their first trimester, you may opt for a mastectomy instead of breast conserving surgery because they won't be able to have radiotherapy in a time.
manner. In addition, a patient in their second or third trimester may be able to undergo breast conserving surgery and then have their radiotherapy once they have delivered that baby. pretty detailed discussions that need to be happening at an MDT between the surgeons, oncologists and radiation oncologists. At the time of surgery, if the patient has a negative axilla preoperatively, then they should be staged with a sentinel lymph node biopsy.
lymphocentigraphy using the technetium-99 is very low-dose radiation and is thought to be safe and feasible. during pregnancy. And you can also use a methylene blue injection to use dual localization of that sentinel node. Moving on now to chemotherapy. Interestingly, you can actually give chemotherapy to a patient who is pregnant in the second and third trimesters.
probably a very small risk to the child. And there was a series of 197 women that were given chemotherapy in their second and third trimesters that demonstrated that there was no... increased risk of malformations, adverse events, or other complications for the infants or newborns. So this is a pretty accepted treatment option. The choice of chemotherapeutic agents may be changed by the oncologists. So for example, methotrexate is not.
good in pregnancy and there may be others that have higher risk so they may change the regime compared to what they would usually give a patient. In addition, when looking at trastuzumab for HER2-positive cancers, this can be associated with oligohydramnios in 50% of cases, so also should be considered. Looking at hormonal therapy... Endocrine therapy, so use of tamoxifen, is not recommended in pregnancy and has a really high association with spontaneous abortions and fetal death.
And another consideration is that if you are giving a patient chemotherapy, it should be stopped three to four weeks prior to delivery so that the patient isn't myelosuppressed for delivery, which would increase their risk of septic and infectious complications. So going through a couple of potential scenarios, if you had a patient in the first trimester with an early breast cancer, you could offer that patient a mastectomy and then...
After delivery of that baby, you could consider other treatments such as hormonal treatment. And if they were going to be found to have high risk features after surgery, then you could consider giving them chemotherapy in their second or third trimester. In a patient who's in their second or third trimester at diagnosis with an early breast cancer, this patient could undergo a mastectomy or potentially breast conserving surgery with a plan for radiotherapy after delivery.
And again, after delivery could be considered for hormonal treatment and potentially undergo chemotherapy if they had really high risk features on their pathology. during their second or third trimester or after they've delivered the baby. In patients with locally advanced or metastatic breast cancer, this is obviously a very difficult issue.
If they're in their second or third trimester, then these patients would be treated with chemotherapy followed by further chemotherapy and surgery, radiotherapy as required after the baby was delivered. So it does by some time. before needing to give some of those other treatments. If they're in their first trimester, then really it's very difficult. There's three options which include termination of the pregnancy with prompt treatment.
administration of chemotherapy with an acceptance of the risk to the fetus. or delaying oncological treatment and understanding that there's associated oncological risks. And in all of these situations, the patient's wishes with regards to the child is going to be really high considering.
when you're planning treatment. So in summary, I've said it once, I'll say it a thousand times, the key for treatment of pregnancy associated breast cancer is that this needs to be multidisciplinary with consideration of all aspects and an individualised treatment plan for that patient. I wanted to briefly touch on premenopausal women who have the potential to become pregnant who are diagnosed with breast cancer. I don't think we need to know a whole heap about this, but...
It's important to consider that these women may plan to have children in the future, and especially if they're going to undergo systemic chemotherapy, that there may be a risk to their ability to do this in the future. So first thing is to identify this problem when you're diagnosing a patient with breast cancer, especially if they're young or premenopausal. You need to consider referral to an obstetrician to consider future options.
The patient will also need information about the likely disease course, survival and recurrence, and this may influence their decision-making in the future to have a family. Specifically, you should counsel these women to avoid... becoming pregnant while they're being treated with chemotherapy, radiotherapy, or tamoxifen. And a proportion of patients will develop amenorrhea or ovarian failure with systemic chemotherapy, especially if they are less than 40 years old. And there was a study
Looking at giving these patients gonadotrophin-releasing hormone agonist, gozarelin, with their chemotherapy to try to reduce the risk of ovarian failure. This is called the POEMS study, Prevention from Early Menopause Study. And they found that if you give these patients gosrelin, that their ovarian failure rate was 8% compared to 22% if they were not given gosrelin and were just given the chemo alone.
In addition, patients could also consider egg harvesting which would give them the possibility of using IVF to become pregnant in the future. The other considerations include whether or not the patient will be able to breastfeed from a breast that has had breast conserving surgery and most likely outcome is that they will be able to breastfeed unless the ducts have been cleared from underneath. the nipple areola complex or the entire breast has been removed as is with a mastectomy.
And also radiation can influence the ability of the patient to breastfeed on that side. So all of these things need to be considered and discussed with the patient and definitely referral to an obstetrician and consideration of the use. of other adjuncts such as gozarelin or referral for egg harvest should be considered. The last special population I want to mention is a group of patients who present with a positive auxiliary node, but unknown or occult primary cancer.
Specifically, we're talking about where the suspicion is based on the appearance of the pathology that this is a breast cancer in the auxiliary node. This is a very rare presentation of breast cancer. Less than 1% of all presentations will be in the axilla with no clear primary and can be thought of as a subs... subgroup of the cancer of unknown primary kind of overall umbrella.
Specifically we're talking about where there's no evidence of a breast lesion or other distant disease after you've completed all of your staging. In terms of the differentials of a malignancy in the axillary lymph nodes or an enlarged lymph node in the axilla, Some could be benign disorders, so reactive or inflammatory lymph node. But if you get a biopsy that shows a probable malignancy, 50% of auxiliary lymph node malignancies will be related to a breast cancer.
Other differentials include lymphoma, melanoma, sarcomas, thyroid cancer, skin cancer metastases, lung cancer metastases, and very rarely other tumors can. spread to the axilla, including uterine, ovarian, or gastric cancers. And in about 30% of cases, the primary site cannot be identified based on looking at that biopsy. So the first step in the workup of a patient with unexplained auxiliary lymphadenopathy is to get a biopsy.
And this can be done via an ultrasound guided FNA or preferably a core biopsy so you can get some information about the architecture of the tumor cells. This is then looked at under hematoxilin and eosin stain and then further immunohistochemistry tests and then... to try and give more information about where these tumour cells could have come from. Especially if the tumour is very poorly differentiated, it can be difficult to tell what the primary tissue was.
In terms of the immunohistochemistry stains that are done, none of the stains that they do alone can be diagnostic of a breast cancer primary, but there are certain patterns of staining that. are more likely to be breast cancer. So this includes tumors that stay positive for CEA, CK7, ER and PR, mammoglobulin, CA125. and BRST2. And they would also stay negative for CK20 and TTF1.
I can go into a little bit more detail about these. I'm not sure whether this would necessarily be required, but CEA you may have come across in staining for breast, lung, and adenocarcinomas, specifically from the GIT origin. CK7 and CK20, so cytokeratin 7, which is usually positive in breast cancer, can also be positive in lung, ovary, and endometrium, but usually not lower GI.
And CK20, which should be negative, is usually found in gastrointestinal epithelium, urothelium, and Merkel cells. ERPR are usually positive in breast cancer, as we already know. BRST2 is a disease fluid protein that's tested on the cell. And in 65% to 80% of the time, this is... positive in breast cancer and can be quite specific for breast cancer. It's rarely positive in skin adenexal tumors, endometrial or salivary gland tumors.
Mammoglobulin is sensitive but not particularly specific for breast cancer. It can also be found in gynae, lung, urothelial, thyroid, colon, and hepatobiliary cancers. TTF1, which was the one that should be negative in breast cancer, is very rarely positive in breast cancer, but can be positive in lung cancers. So CA125 can be positive in breast and ovarian cancers. Not usually, about 10% of breast cancers will be positive for CA125.
And we can also do immunohistochemistry for HER2, which isn't particularly helpful in diagnosis as only 18 to 20% of breast cancers are HER2 positive, but is always done to guide treatment as we've talked about previously. So again, I don't know how much information we'll need about all that, but just to summarize again, breast cancers are usually show a pattern of positivity for CEA, cytokeratin 7, ERPR, mammoglobulin. CA125 and BRST2 proteins and negative for CK20 and TTF1.
After the biopsy has been taken, a thorough imaging workup should be done to identify whether there is a primary breast tumor. And this would be starting simply with a mammogram and ultrasound if these have not been done already. And if both of these are negative and no primary tumor is found, then these patients should go on to have a breast MRI. They also need staging because they have auxiliary spread. So these patients need a CT chest, abdo, pelvis, and a bone scan, plus or minus a PET scan.
These patients' management should be guided by what you've found. So if you cannot find a tumour in the breast, then you would proceed as I'm about to talk about. But if you do find a breast cancer or a tumour in the breast, you should manage them as we've already talked about for management of breast cancer. But specifically talking about patients where you've done all of that staging and an MRI of the breast and you cannot find a primary tumor.
So the exam answer is that these patients should undergo local regional surgery with an auxiliary lymph node dissection. And this is important for local control, for giving more information about the lymph nodes, for... giving prognostic information about how many nodes are involved and to help guide your treatment. What to do with the breast is potentially controversial. Probably the exam answer would be that you would do a mastectomy.
In 65% of cases, a breast malignancy is then found on close histological review of the breast. There's been some studies that have shown that there's a lower rate of local recurrence in the breast as well as disease-free and overall survival if you do a mastectomy. And there is some indication for post-mastectomy radiotherapy to enhance local control if there's more than four lymph nodes involved or equal to or more than four lymph nodes involved.
Some patients may undergo an observation-only approach. In some studies, I've seen this happen, but this has a high risk of local recurrence and it's not really recommended, so I wouldn't use that as an exam answer. And the other thing that I saw was whole breast radiotherapy, which again, there's some studies looking at that, but probably the safest answer would be to do a mastectomy. Patients can then undergo systemic chemotherapy.
There's not great studies looking specifically at breast cancer in lymph nodes with an occult malignancy, but we extrapolate treatment from the modern treatment protocols. So we're talking about a lymph node positive breast cancer. patients would have chemotherapy and you would treat them based on the tumor biology and hormone receptor status as you would breast cancer.
In patients with a HER2 positive tumour, you would give them trastuzumab. And if the patient's tumour was hormone receptor positive, then you would also offer them adjuvant endocrine treatment. The five-year survival for these patients ranges between 60% and 93% and depends on the number of lymph nodes involved, the higher number of lymph nodes involved, the worse the prognosis.
And obviously, if there is any evidence of metastatic disease on your staging, then you would treat this patient as a metastatic breast cancer. And that's all I have time for today about special populations in regards to breast cancer. Please remember to rate, review and subscribe so other people are able to find the podcast.
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